Mindfulness Intervention Decreases Frequency and Severity of Flares in Inactive Ulcerative Colitis Patients: Results of a Phase II, Randomized, Placebo-Controlled Trial

Abstract

Background

Ulcerative Colitis (UC) is a chronic, inflammatory disease, characterized by symptomatic periods (flare) interspersed with asymptomatic periods (remission). Evidence suggests that psychological stress can trigger flare. Studies have shown that mindfulness interventions (MI) reduce stress, foster more adaptive coping, and improve quality of life, but have been minimally used for UC patients. The objective of this study was to determine whether participation in an MI results in improvements in UC disease course and inflammatory cascades, mindfulness, perceived stress, and other psychological outcomes in inactive UC patients with limited or no exposure to past MI.

Methods

Participants were randomized to an 8-week MI or control group. Biological and psychological assessments were performed at baseline, post 8-week course, and at 6- and 12-months.

Results

Forty-three participants enrolled. The MI increased the state of mindfulness and mindfulness skills, decreased perceived stress and stress response in patients with inactive UC. The MI intervention significantly decreased the incidence of flare over 12 months (P < .05). None of the UC patients in the MI flared during 12 months, while 5 of 23 (22%) control group participants flared during the same period.

Conclusions

MIs could be considered as adjuvant treatment for a subset of UC patients with high perceived stress and low state of mindfulness.

The trial was registered at clinicaltrials.gov as NCT01491997.

Introduction

Ulcerative colitis (UC) is a chronic, inflammatory disease that is characterized by symptomatic periods (flare) interspersed with asymptomatic periods (remission). During flare, patients suffer from disabling symptoms (e.g., bloody diarrhea, abdominal pain, urgency, fecal incontinence, arthritis and/or arthralgia, fatigue, and fever), impaired quality of life, loss of time from work or school, and potentially requiring hospital admission and/or surgery. Thus, a major goal of the management of UC to is to prevent flare and maintain remission. To achieve this goal, it is necessary to identify and prevent or modify triggers for disease flare as much as possible. The most well-established modifiable factor that can impact disease activity in inflammatory bowel diseases (IBD) is tobacco use, which has a discordant impact and clearly worsens disease activity in Crohn’s disease but is associated with a decreased risk of flares in UC.^1,2 However, other factors are also important in determining the risk of flares.

There is evidence suggesting that psychological stress can trigger a UC flare.^3–6 Additionally, UC patients demonstrate an exaggerated physiological response to stress,^7,8 and psychological stressors can initiate mucosal and systemic inflammatory cascades.⁸ Given these associations, improving stress management may be a viable preventative approach for UC flares. Traditional Western-based treatment for anxiety and depression is cognitive-based therapy (CBT), but recently mindfulness interventions (MI) have incorporated Eastern medicine–based principles of mindfulness in CBT. There is strong empirical evidence to support the effectiveness of MI for reducing stress. Mindfulness-based interventions, which are derived from Buddhist philosophy and traditions, seek to decrease suffering and improve well-being.⁹ These interventions focus on increasing mindfulness, which is defined as intentionally focusing one’s attention on the present moment in a nonjudgmental way.¹⁰ Studies have shown that MI reduce stress, foster more adaptive coping, and improve quality of life among a wide range of medical and nonmedical populations.^11–15

The utility of MI for patients with IBD has not been widely explored.¹⁶ We previously reported the results of a phase II clinical trial assessing the effects of Mindfulness-Based Stress Reduction (MBSR), a widely used curriculum for teaching mindfulness,¹⁰ on the UC disease course.¹⁷ In 55 patients with inactive UC, MBSR improved the quality of life, but did not have a significant effect on participants’ state of mindfulness, level of perceived stress, or the frequency or severity of UC flares. These results were in contrast to studies using MBSR in other patient populations, which have consistently found positive effects on mindfulness¹⁸ and stress reduction.^19,20 It is possible that results in our trial were due to low levels of stress and relatively high levels of mindfulness in participants at baseline, which likely contributed to a ceiling effect for the MBSR intervention. In addition, this trial did not exclude participants who had previously participated in meditation, yoga, or psychotherapy, which may have contributed to the relatively high mindfulness and low perceived stress scores at baseline and a selection bias in patients who were interested in MI. In support of this conclusion, we found a positive effect of MBSR among participants with either a high level of perceived stress, high cortisol levels, or severe gastrointestinal symptoms at baseline.¹⁷

To determine whether the results of our analysis can be used prospectively and to confirm that MI can be effective in a subset of patients with inactive UC and a limited history or no history of MI, we conducted another phase II, randomized, time- or attention-controlled trial. The primary endpoint for this clinical trial was a decrease in the frequency of UC flares (total Mayo score) during the 1-year study. Secondary outcomes included changes in (1) UC disease activity; (2) markers of intestinal and systemic inflammation; (3) mindfulness scores; (4) perceived stress; and (5) other psychological outcomes. The results from this trial indicate that MI significantly decreased the frequency of UC flares over the 12-month study period.

Methods

Study Design

This was a phase II, randomized, time- or attention-controlled trial in patients with inactive UC, including an 8-week intervention and a 1-year follow-up period. Study visits occurred before the intervention, within two weeks after the 8-week intervention, and at 6 and 12 months after the intervention.

Study Participants

Inclusion criteria

Participants were included if they met the following criteria:

1. Biopsy-confirmed UC;

2. Inactive disease at the time of recruitment (Mayo score ≤ 2 with an endoscopy score of 0 or 1);

3. At least 1 physician-documented flare within the past 18 months;

4. 18–80 years of age;

5. Left-sided or pan-colonic disease (Montreal E2/E3);

6. Either taking no IBD medication or on a stable dose of UC medication (oral 5-ASA [aminosalicylic] products [Mesalamine, Sulfasalazine, Colazal] for at least 3 weeks prior to enrollment; immunomodulators [Azathioprine/6 mercaptopurine, methotrexate] or biologics [tumor necrosis factor antibody] for at least 8 weeks prior to enrollment; or prednisone ≤ 20 mg a day for at least 3 weeks prior to enrollment); and

7. Willingness to participate in an 8-week course of study intervention.

If patients were taking maintenance oral 5-ASA or immunomodulators or biologic products, they were instructed to stay on the current dose over the course of the study, and any changes in dose were recorded. Patients who were taking prednisone were allowed to wean off prednisone per physician instructions. A psychologist interviewed all prospective patients to screen them for psychiatric eligibility (see exclusion criteria).

Exclusion criteria

Participants were excluded if they met any of the following criteria:

1. History of colon resection;

2. Ulcerative proctitis with colonic involvement <15 cm from the anus;

3. Crohn’s colitis or indeterminant colitis;

4. Use of antibiotics within the previous 14 days prior to enrollment;

5. Nonsteroidal anti-inflammatory drug use >3 days/week (daily use of baby aspirin acceptable);

6. Use of anticoagulants and antiplatelet drugs;

7. Abnormal bleeding (prolonged International Normalized Ratio/INR), or history of easy bruising or bleeding (except for rectal bleeding during a flare);

8. Chronic, severe disorders, such as cardiac disease (New York functional state score > 3), renal disease (creatinine >3 mg/dL), pulmonary disease (shortness of breath at rest), requirement for oxygen use (not including asthma), active infection, or other organ system disease or morbidity requiring medical visits >3 times/year or any condition that creates excess perceived stress as determined by a psychologist;

9. Unresolved history of physical or sexual abuse;

10. Current or previous diagnosis of a dissociative disorder, such as borderline personality disorder or posttraumatic stress disorder; history of psychosis; hospitalization for self-harm or suicidal ideation; or current, severe psychiatric disorder, including major depression with suicidal ideation, new psychiatric treatment (patients were eligible if they had been seeing a psychologist or psychiatrist at constant intervals throughout the past 6 months and were not involved in a mindfulness or meditation “treatment,” “training,” or “group”);

11. Current use of illicit substances (regular use of marijuana acceptable);

12. Resistance to mindfulness training due to religious or moral beliefs or other reasons;

13. Current pregnancy or lactation; or

14. Had previously undergone mindfulness training or had learned or used other forms of mind-body techniques (did not include yoga and unstructured self-help techniques).

Intervention

Experimental group: MI

The MI was administered by a psychologist with training in MBSR, and closely mirrored the curriculum of the Center for Mindfulness in Medicine, Health Care, and Society at the University of Massachusetts Medical School.¹⁰ The MI used a group format and consisted of 8 weekly sessions that were each 1.5 to 2 hours long. Weekly sessions involved instruction and practice in formal (meditation, yoga) and informal (awareness of personal reactions to everyday events) mindfulness practices. A voluntary 4-hour half-day retreat was offered between sessions 6 and 7, which focused on practice of formal meditations. Participants were given weekly homework assignments, intended to reinforce practices and concepts introduced during group sessions. Adaptations to standard MBSR (including shortened weekly sessions, offering a shortened voluntary retreat) were made to account for very small class sizes.

Time or attention control group

Patients randomized to the time or attention group attended sessions with a group format similar to that of the MI group. Weekly sessions were moderated by a clinical psychologist, who provided structured lectures focused on general aspects of physical and psychological health (not IBD-focused), and the other 2 weeks of the 8 week course were comprised of a video presentations.¹⁷ Topics include: the origins of physical illness, the impact of stress on physical health, exercise, and risk factors for cardiovascular disease. The course did not include information on UC and did not teach skills for coping with stress. The psychologists who facilitated the MI differed from the psychologists who facilitated the control group (no overlap).

Assessments

Participants were assessed at baseline (visit 1; preintervention), after the 8-week course (visit 2) and at 6- and 12-month follow-ups (visits 3 and 4) at Rush University Medical Center. Participants completed a series of structured, validated questionnaires (see below for details) to assess UC disease activity, IBD-specific quality of life, and psychological parameters. Each participant was also interviewed and examined by a study physician (A.K. or G.S.) and was assessed by a study psychologist (S.H. or designee) who was not an instructor for either the MI or the control group. Each participant provided stool and 24-hour urine samples (collected at home the day before each study visit and brought to the study visit). Urine volume was recorded, and urine and stool samples were aliquoted and stored at –80 ºC for future analysis. Participants also had a blood draw, and serum and plasma were stored at –80 ºC for future analysis.

Participants were instructed to inform the clinical coordinator if they developed any new symptoms, including an increase in the frequency of bowel movements, changes in stool consistency, urgency, and bleeding that would a suggest UC flare. If the participant experienced symptoms that might suggest a UC flare, the clinical coordinator arranged a study visit within 7 days of being informed of new symptoms. The study physician (A.K. or G.S.) evaluated patients and performed an unprepped sigmoidoscopy to evaluate whether the participant experienced a flare. The treating physician for each participant who developed a flare during the 12-month study period was immediately informed, and the participant was treated per physician instructions. Participants who had a flare during the 12-month study period were asked to continue the study and have their regular follow-up study visits at 6 and 12 months.

Outcomes

Primary outcome

The primary outcome was frequency of UC flares based on Mayo score UC disease activity. A UC flare was defined as a Mayo score Disease Activity Index (DAI) value for UC of 3 or greater plus a sigmoidoscopy score of 2 or 3 (see below).

The Mayo score DAI for UC

The Mayo score DAI²¹ includes stool frequency, rectal bleeding, endoscopy score, and global assessment by a physician. The Mayo score DAI ranges from 0 to 12, with higher scores indicating greater disease activity.

Secondary outcomes

Secondary outcomes include changes in: (1) UC disease activity; (2) markers of intestinal and systemic inflammation; (3) mindfulness scores; (4) perceived stress or stress response; and (5) mindfulness and other psychological outcomes.

Modified UC-DAI

The UC-DAI²² accounts for overall well-being; the presence of abdominal pain; bowel movement frequency; stool consistency; bleeding; anorexia; nausea or vomiting; abdominal tenderness; eye, joint, mouth, or skin complications; and fever. We also assessed the presence and severity of urgency. Scores range from 0 to 30, with higher scores indicating a greater disease burden.

The Inflammatory Bowel Disease Quality of Life Questionnaire

The Inflammatory Bowel Disease Quality of Life Questionnaire (IBDQ)^23,24 is a 32-item, disease-specific questionnaire used to assess the health-related quality of life in IBD patients. The questionnaire assesses bowel symptoms, systemic symptoms, emotional factors, and social factors. Scores range from 32 to 224, with higher scores representing better health.

Markers of Intestinal Inflammation

Stool calprotectin

Stool calprotectin was used to assess “subclinical” disease activity. Calprotectin was measured via enzyme-linked immunosorbent assay (ELISA; Buehlman fCAL Catalog # EK-CAL-U). Intestinal inflammation was categorized as follows: <50 μg/g indicated no colon inflammation, 51–150 μg/g indicated mild colon inflammation, 151–250 μg/g indicated moderate colon inflammation, and >251 μg/g indicated severe colon inflammation.

Marker of systemic inflammation: serum cytokines and C-reactive protein

Cytokines measured included: interleukin (IL) 6 (Kit: Human Quantikine HS ELISA, Catalog Number HS600B, R&D Systems; Range: 0.156–10 pg/ml) and IL-8 (Quantikine HS ELISA, high sensitivity, Catalog # HS800, R&D Systems; Range 1–64 pg/ml). C-reactive protein (CRP) was measured by Quest Diagnostics (reference range < 8.0 mg/L).

Endoscopic and histology scores

The Mayo Endoscopy Index²⁵ was used to evaluate endoscopic disease activity, and the index was graded as follows: 0 indicated a normal mucosal pattern; 1 indicated mucosal erythema, slight edema, and red spots; 2 indicated superficial erosions, friable mucosa with bleeding upon touch, and minimum spontaneous bleeding; and 3 indicated marked spontaneous bleeding, severe mucosal ulcerations, and large amounts of mucopurulent discharge. Endoscopic grades of 2 or 3 are considered active disease and UC flares.

Geboes score

The Geboes score²² is a histological assessment score that evaluates the degree of goblet cell depletion, inflammatory cell infiltration, superficial epithelium modifications, ulcerations, crypt shape, and crypt abscesses. Scores range from 0 (normal) to 3 (severe inflammation), according to both endoscopists and pathologists who were blinded to the group assignment.

Perceived Stress Questionnaire

The Perceived Stress Questionnaire (PSQ)²⁶ is a validated measure of perceived stress that has been used in patients with gastrointestinal disorders.^27,28

Urinary cortisol was assessed as a physiological measure of stress reactivity from urine collected over a 24-hour period prior to each study visit (R&D Systems, Inc., #KGE008B, assay range: 0.156–10 ng/ml).

Mindfulness and Psychological Outcomes

The 5-Facet Mindfulness Questionnaire

The 5-Facet Mindfulness Questionnaire (FFMQ)²⁹ assesses multiple facets of mindfulness, including observing, describing, acting with awareness, nonjudging the inner experience, and nonreactivity to the inner experience.

The Beck Depression Inventory

The Beck Depression Inventory³⁰ is used to assess depression. Scores range from 0 to 63.

The State-Trait Anxiety Inventory

The State-Trait Anxiety Inventory (STAI)³¹ evaluates anxiety. This assessment focuses on the cognitive symptoms of anxiety to avoid confounding with somatic symptoms related to disease. The state anxiety component of this measure was used in this trial.

The Pittsburgh Sleep Quality Index

The Pittsburgh Sleep Quality Index³² assesses sleep over the previous 4 weeks, including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction.

The Expectancy and Credibility Questionnaire

The Expectancy and Credibility Questionnaire (ECQ)³³ measures treatment expectancy and rationale credibility and has been used in many treatment outcome trials. Participants in both groups completed the ECQ both before and after treatment, to determine the role that the expectancy and rationale credibility constructs play in the outcomes and to confirm that the participants were blinded to our hypothesis.

All outcome measures can be found in Appendix 1.

Randomization

The study statistician (T.B.) (who was not blinded to group assignment) created a list based on permuted, variably sized, block randomization of at least 100 participants with block sizes of 4 and 6 for a 2-arm study. Variably sized, block randomization was used so that the clinical investigators were blinded to the block size. We used R version 2.15.1 (R Studio) and library “blockrand” to perform participant randomization. We created a pdf file of randomized cards based on the randomized allocation. These files were printed, and cards for each patient were put into sealed envelopes for the study coordinator once the patients met the eligibility criteria. The maximum time between random assignment of intervention by the study coordinator and the study intervention was 4 weeks.

Data and Statistical Analysis

Power analysis

We predicted that UC flares would be common in this participant cohort (see the inclusion and exclusion criteria), because UC flares occurred in over half of participants in our phase II clinical trial assessing the effects of Mindfulness Based Stress Reduction (MBSR; ¹⁷). The power analyses, assuming an α of 0.05 for all tests, indicated that for models involving analyses of correlational data, there will be sufficient power at even small effect sizes for the smallest possible sample with full data across all data points and virtually all variables. For the most conservative estimate, we based our calculations on having 50 participants with data with full integrity. With an effect size (r) of 0.15 and 50 participants, power is 80 or greater to detect effect sizes of 0.20. Effect sizes below this threshold would likely not be clinically significant or substantively interpretable, as they would explain less than 2% in the variance of the dependent variable. Thus, most effect sizes that would be reasonably and substantially interpretable and will have good power. Each factor that is suspected of varying between groups can be examined with the chi-square test based on 1 degree of freedom, by setting it invariant in 1 model and then allowing it to be freely estimated in the other. Such a chi-square test provides a power of 0.80 with an effect size difference of 0.15. For binary categorical measures, such as responsiveness to the MI, we conducted separate power analyses.

The power for adjusted analyses of primary predictors of interest was evaluated as a function of the risk of the outcome when all ancillary variables are set to their mean value, the predictor is set to the mean value, the proportion of variance in the predictor is explained by the ancillary variables, and the odds ratio of the outcome variable increases the predictor by an amount equal to 1 of its standard deviation. The range in probabilities of outcome variables can be anywhere from 20% for less likely events to 50% for more likely events, and we provide power calculations over a wide range of probabilities. We believe that the amount of variation of our typical model ranges from about 20% to 50%. Appendix 2 contains additional information representing the minimum odds ratio than can be detected with 80% power, which indicates sufficient power for the expected changes in the primary outcome.

Statistics

First, t-tests and chi-square tests were used to test for baseline differences in demographic characteristics, as well as calprotectin, quality of life (total and subscale scores), perceived stress, urinary cortisol, and mindfulness subscale scores. Next, the effects of the intervention over time were analyzed using generalized estimating equations (GEE). A GEE model was used to determine differences between the MI and the control groups at each study visit. An advantage about the GEE method is that it utilizes information from incomplete observations when data are missing, allowing us to use all observations. A Kaplan-Meier plot was generated to examine the time until a subsequent UC flare. The log-rank test was then used to compare differences by intervention group. Data were analyzed using SAS 9.4 (SAS Institute).

Ethical considerations

The Rush University Medical Center Institutional Review Board approved this study, which was registered at clinicaltrials.gov as NCT01491997. Participants provided written consent and received a verbal explanation and written information regarding the study. Patients were compensated a total of $600 USD for participation in the study, which was disbursed upon completion of the study. Participants were compensated ($200 USD) upon completion of the 8-week mind and body intervention ($200); at completion of the 6-month follow-up visit ($200 USD); and at completion of the 12-month follow-up study visit ($200 USD). This compensation was appropriate based on the extensive time and effort required to participate in 8 classes, including weekly homework; to complete 4 study visits that included at-home collection of stool and urine and in-clinic blood collection and flexible sigmoidoscopy; and to complete the questionnaires. An independent Data Safety Monitoring group met regularly throughout the study, to ensure that there were no adverse events.

Results

Participants

Figure 1 depicts recruitment eligibility and screening. Forty-three participants with inactive UC (based on Mayo score DAI values) were included in this intention-to-treat analysis. Table 1 lists study participant demographic characteristics at baseline according to randomization. The participants were 58% female, and 72% identified as White, 11% as Black or African American, 14% as Hispanic, 3% as other or multiple races. The mean age was 41.6 ± 12.3 years. Groups did not differ by age, extent of disease, number of flares in the past year, prednisone dependence, or number of classes attended. Compared to the time or attention control arm, MI participants were significantly older when diagnosed with UC. There were no other significant differences. There were no differences by groups in the ECQ results at visit 1 (P = .582) or visit 4 (P = .156), suggesting integrity of blinding of the study participants.

Figure 1.

Recruitment eligibility and screening. Abbreviation: MI, mindfulness-based intervention.

Table 1.

Participant characteristics, disease-related factors, and study participation^a

	Mindfulness Intervention (n = 20)	Active Control (n = 23)	p-value
Participant Characteristics
Age, years	44.8 (13.5)	38.7 (10.5)	.12
Sex, % female	9 (50%)	13 (65%)	.35
Ethnicity			.63
White, %	16 (89%)	17 (85%)
Black/African American, %	2 (13%)	2 (11%)
Hispanic, %	1 (6%)	4 (21%)
Other/multiple races, %	0 (0%)	1 (5%)
Disease-Related Factors
Age at diagnosis, years	37.7 (12.2)	27.9 (10.3)	.01
Number flares in past year	2.8 (6.8)	2.1 (1.9)	.66
Extent of disease
Left-sided	8 (40%)	10 (43%)	.82
Pancolitis	12 (60%)	13 (57%)
Prednisone-dependent, yes	7 (35%)	11 (48%)	.40
Medication at baseline, yes
None	0	1 (4%)	1.00
Steroids	2 (10%)	3 (14%)	.35
5-ASA	17 (85%)	17 (77%)	.47
Immunomodulators	4 (20%)	7 (32%)	.50
Biologics	5 (25%)	5 (23%)	1.00
Antibiotics	0	0	n/a
Study Participation
# Classes Attended	5.7 (2.7)	5.5 (2.4)	.82
Markers of Inflammation
CRP, mg/L	0.21	0.45	.22
Calprotectin, μg/g	277.43 (548.6)	342.34 (554.26)	.47
Disease Activity
UC-DAI	3.41 (3.0)	3.46 (2.1)	.59

Data are from t-test and chi-square comparisons by group.

Abbreviations: 5ASA, 5-aminosalicyclic acid; n/a, not applicable.

Is a Mindfulness Intervention an Appropriate Approach to Positively Impact the UC Disease Course?

Impacts of stress on intestinal inflammation

We assessed whether the biological response to stress is correlated with intestinal inflammation, even when patients are in clinical remission. We found that calprotectin was positively correlated with urinary cortisol (r = 0.37; P = .02) among our sample at baseline. This supports our original hypothesis that an intervention that targets stress reduction would impact the UC disease course.

Impacts of MI on the state of mindfulness

Next, we determined whether mindfulness (FFMQ) was correlated with stress (PSQ).

We found an inverse correlation (r = −0.54; P = .0005) between the 2 variables. This justifies our hypothesis that the MI has the potential to increase mindfulness and reduce stress.

We then determined whether mindfulness classes were successful, and whether our intervention achieved the stated goal and was able to improve the state of mindfulness of the participants. Thus, we used the FFMQ instrument to determine whether participation in MI led to changes in the state of mindfulness. In the MI group, mindfulness (FFMQ) scores increased significantly on all subscales, with the exception of the describing subscale (Table 2). Specifically, mindfulness was increased compared to baseline for the FFMQ observing subscale at the 8-week (P < .01), 6-months (P = .01), and 12-month (P < .01) visits; the FFMQ acting with awareness subscale at the 8-week (P < .01) and 12-month (P < .01) visits; the FFMQ nonjudging of the inner experience subscale at the 6-month (P = .01) and 12-month (P = .01) visits; and the FFMQ nonreactivity to inner experiences subscale at the 8-week (P < .01) and 12-month (P = .01) visits. There were no significant group-by-time interactions on any of the FFMQ subscales at any time point. These findings clearly showed that the MI was effective and improved the state of mindfulness and mindfulness skills of the participants.

Table 2.

Mindfulness GEE Means and Standard Errors From the FFMQ’s 5 Subscales

	Baseline	Postintervention (8 Weeks)	6-Month Follow-Up	12-Month Follow-Up
FFMQ: observing
Control	26.00 (1.91)	25.57 (1.49)	25.82 (1.66)	26.00 (1.91)
Mindfulness intervention	23.56 (1.52)	28.40 (1.37)a	25.90 (1.45)a	26.74 (1.38)a
FFMQ: acting with awareness
Control	29.23 (1.69)	28.97 (1.78)	29.29 (1.38)	30.47 (1.51)
Mindfulness intervention	26.39 (1.38)	29.78 (1.24)a	28.09 (1.08)a	29.41 (1.45)a
FFMQ: nonjudging of inner experience
Control	30.77 (1.54)	33.94 (1.21)a	33.33 (1.37)	33.72 (1.28)
Mindfulness intervention	30.83 (1.50)	33.41 (1.63)	33.35 (1.35)a	33.76 (1.11)a
FFMQ: nonreactivity to inner experience
Control	22.34 (1.04)	22.16 (1.16)	22.75 (1.05)	22.52 (1.38)
Mindfulness intervention	20.83 (0.89)	23.62 (1.20)a	22.80 (1.18)	23.50 (1.07)a
FFMQ: describing
Control	29.70 (1.34)	31.04 (1.56)	30.58 (1.43)	30.79 (1.72)
Mindfulness intervention	29.56 (1.34)	29.86 (1.51)	28.92 (1.61)	29.41 (1.74)

All numbers reflect GEE estimate values.

Abbreviations: FFMQ, 5-Facet Mindfulness Questionnaire; GEE, generalized estimating equations.

What are the Impacts of MI on the UC Disease Course?

Primary outcome: effects of MI on frequency of UC flares

We aimed to determine whether participation in the MI was protective against subsequent UC flares, as defined by the Mayo UC DAI. None of the 20 UC patients randomized to the MI arm flared during the 12-month course of the study, while 5 of 23 patients (22%) randomized to the time or attention control group flared between the baseline and 12-month follow-up assessments (Figure 2). Thus, the MI significantly (P < .05) decreased the incidence of flares over 12 months. Table 3 depicts UC-related data, markers of inflammation, mindfulness, and stress data (at baseline and at the time of flares) for these 5 participants who experienced a flare during the study period. The subjects who flared were all Caucasian, ranged in age from 27 to 62, were predominantly female (n = 4), and were diagnosed with UC between the ages of 9 and 35 years.

Figure 2.

Time to flare in the MI and control groups. Abbreviation: MBSR, Mindfulness-Based Stress Reduction; MI, mindfulness-based intervention.

Table 3.

Flare Subject Characteristics^a (n = 5)

	Subject A		Subject B		Subject C		Subject D		Subject E
	BL Visit	Flare Visit	BL Visit	Flare Visit	BL Visit	Flare Visit	BL Visit	Flare Visit	BL Visit	Flare Visit
Markers of inflammation
Calprotectin	592.89	598.00	277.34	337.39	50.95	406.30	43.74	457.35	28.55	631.67
CRP	0.59	0.5	0.34	0.58	0.19	0.37	0.05	0.05	0.11	0.21
IL-6	1.71	2.77	1.47	1.53	1.33	4.34	0.43	0.71	0.83	1.56
IL-8	3.48	3.98	2.33	5.84	6.20	23.50	1.64	2.10	1.79	2.85
UC disease activity
Sigmoidoscopy score	1	2	0	3	1	2	1	2	0	2
Bleeding score	0	1	0	2	0	0	0	1	0	0
Mayo score	2	5	0	6	1	3	2	5	0	3
UC-DAI	5.71	3.71	1	5	2.14	2.57	3.86	7.71	4	2
Mindfulness and stress
Mindfulness, FFMQ	-	-	191	187	130	143	107	143	103	128
Anxiety, STAI	0.16	0.46	0.01	0.09	0.48	0.29	0.48	0.18	0.57	0.47
Urinary cortisol	79.84	67.87	104.92	13.34	41.71	75.79	62.92	49.88	39.37	63.04

Abbreviations: BL, baseline; CRP, C-reactive protein; DAI, Disease Activity Index; FFMQ, 5-Facet Mindfulness Questionnaire; IL, interleukin; STAI, State-Trait Anxiety Inventory; UC, ulcerative colitis.

Secondary outcomes

To assess the impacts of the MI on patients who did not flare, we assessed several parameters of remission, including clinical remission (Mayo score < 2), endoscopic remission (endoscopic Mayo score < 2), histological remission (histology score < 2), and deep remission (Mayo endoscopy score = 0 and histology score < 2). Observations after the flare (Tables 4 and 5) were excluded, because these patients received interventions, like prednisone, to treat their flare up and these interventions likely influenced their following biomarker/endoscopic/histological results. Appendix 3 includes results that include these excluded observations. This analysis revealed no significant differences between the 20 patients in the MI group and 18 patients in the control group who had no clinical flare during the 12-month study period (Table 4). However, there was a trend for increased histological and deep remission in the MI group at the 8-week and 6-month follow-up visits.

Table 4.

Changes in Remission Across Time in Those UC Patients Who Did Not Experience a Flare^a (n = 18)

	Preintervention (Visit 1)			Postintervention (8 Weeks; Visit 2)			6 Months (Visit 3)			12 Months (Visit 4)
	Control	MI	P Value	Control	MI	P Value	Control	MI	P Value	Control	MI	P Value
Clinical remission, n (%)	16 (88.9)	18 (90.0)	.3938	13 (92.3)	15 (93.8)	.5149	13 (86.7)	15 (93.8)	.3737	11 (91.7)	15 (93.8)	.5079
Endoscopic remission, n (%)	18 (100)	20 (100)	-	14 (100)	16 (100)	-	14 (100)	15 (93.8)	.5333	11 (100)	16 (100)	-
Histological remission, n (%)	13 (72.2)	17 (85.0)	.1997	10 (71.4)	15 (93.8)	.1124	12 (85.7)	15 (93.8)	.3586	11 (100)	14 (93.3)	.4769
Deep remission, n (%)	12 (66.7)	12 (60.0)	.2418	10 (71.4)	14 (87.5)	.2023	10 (71.4)	14 (87.5)	.2023	10 (90.0)	11 (73.3)	.2283

Clinical remission was defined as a Mayo score DAI < 2. Endoscopic remission was defined as an endoscopic Mayo score < 2. Histological remission was defined as a histology score < 2. Deep remission was defined as a Mayo endoscopy score of 0 AND histology score < 2. Abbreviations: DAI, Disease Activity Index; MI, mindfulness-based intervention; UC, ulcerative colitis.

Table 5.

GEE Means and Standard Errors^a

	Baseline	Postintervention (8 Weeks)	6-Month Follow-Up	12-Month Follow-Up
UC-DAI
Control	0.73 (0.26)	0.90 (0.34)b	1.4 (0.45)	1.2 (0.40)
Mindfulness intervention	0.90 (0.24)	0.48 (0.24)	0.60 (0.23)	0.60 (0.22)
Urgency
Control	0.50 (0.11)	0.57 (0.17)	0.70 (0.19)	0.40 (0.19)
Mindfulness intervention	0.48 (0.17)	0.40 (0.14)	0.37 (0.12)	0.45 (0.13)
Sigmoidoscopy score
Control	0.43 (0.28)	0.27 (0.46)	0.48 (0.28)	0.55 (0.35)
Mindfulness Intervention	0.30 (0.34)	0.08 (0.76)	0.20 (0.63)	0.32 (0.35)
Histology score
Control	1.22 (0.24)	1.11 (0.21)	1.04 (0.31)	0.89 (0.25)
Mindfulness intervention	0.90 (0.28)	0.56 (0.27)	0.68 (0.27)	0.63 (0.23)
Calprotectin
Control	342.34 (120.80)	324.31 (95.96)	289.76 (105.28)	314.96 (117.63)
Mindfulness intervention	277.43 (125.67)	291.97 (118.49)	287.18 (107.34)	351.82 (139.03)
IL-6
Control	2.54 (0.57)	2.15 (0.38)	2.54 (0.52)	2.12 (0.28)
Mindfulness intervention	1.97 (0.27)	2.09 (0.41)	2.07 (0.36)	2.39 (0.61)
IL-8
Control	8.96 (3.58)	6.68 (2.12)	9.32 (3.35)	9.71 (3.32)
Mindfulness intervention	5.03 (1.06)	4.26 (0.47)	4.88 (0.67)	4.73 (0.68)
CRP
Control	0.45 (0.36)	0.28 (0.13)	0.28 (0.18)	0.70 (0.48)
Mindfulness intervention	0.21 (0.21)	0.26 (0.33)	0.27 (0.22)	0.40 (0.32)b

All numbers reflect GEE estimate values. Abbreviations: CRP, C-reactive protein; DAI, Disease Activity Index; GEE, generalized estimating equations; IL, interleukin; UC, ulcerative colitis.

P < .05.

Effect of MI on UC symptoms

We determined whether participation in the MI led to changes in UC-associated symptoms. Here, we used the modified UC-DAI because it contains more detailed symptoms with a larger value range (0–30) compared to the Mayo score DAI that we used to define UC flares. There were no significant differences in UC-DAI scores between the MI and control group patients who did not flare during the course of the study (Table 5), over the course of 12-month study period. The MI had no significant effect on any of the individual symptom scores. There was also no significant difference in urgency scores between participants in the MI and control classes (Table 5).

Effects of MI on endoscopic mucosal healing

We used the Mayo sigmoidoscopy score to determine the impacts of the MI on endoscopic healing, which was part of the inclusion criteria at enrollment. All 20 patients in the MI group had evidence of mucosal healing (score 0−1) throughout the study. Of the 23 patients in the control group, the 5 with UC flares had scores of 2 or 3 (Table 3). Overall, there were no significant difference in sigmoidoscopy scores between the 20 participants in the MI class and the 18 participants in the control class who had no UC flare (Table 5).

Effects of MI on markers of intestinal and systemic inflammation

The effects of the study intervention on the severity of intestinal inflammation was assessed using stool calprotectin. Twelve of 20 (Calprotectin data were not recorded for 3 participants in the control group) participants in the MI class and 14 of 23 (Calprotectin data were not recorded for 2 participants in the mindfulness-based intervention group) participants in the control class had elevated stool calprotectin at the start of the study, and thus they had evidence of ongoing subclinical colon inflammation in spite of being in clinical and endoscopic remission. Three of 5 patients in the control group had normal calprotectin at baseline, and their stool calprotectin increased during their flare (Table 3). Overall, stool calprotectin was elevated throughout the study period in both groups, but there were no significant differences in stool calprotectin levels or in mean change in calprotectin between the 20 participants in the MI class and the 18 participants in the control class who did not develop a flare during the 12-month study period (Table 5).

The effects of the study intervention on the severity of systemic inflammation were assessed using CRP and serum levels of proinflammatory cytokines IL-6 and IL-8. None (C-reactive protein was not recorded from 1 participant in the mindfulness-based intervention class and from 1 participating in the control group) of the 20 participants in the MI class and none of the 23 participants in the control class had elevated CRP or serum at the start of the study. These markers of systemic inflammation were normal throughout the study period, with no significant differences between the 2 groups (Table 5).

Effects of MI on quality of life

We aimed to determine whether the MI affected participant quality of life. Analyses indicated that in the MI group, IBDQ scores improved compared to baseline (Table 6). Significant improvements were in the IBDQ emotional health subscale (at 8 weeks, P < .01; at 12 months, P = .02). In the control group, there were significant improvements in the IBDQ systemic systems subscale (at 12 months, P = .16) compared to baseline. There were no other changes in the quality of life in control participants. There were no group-by-time interactions on the IBDQ total score or any of its subscale scores at any time point (Table 6). These data suggest that the MI improves some aspects of quality of life in individuals with UC.

Table 6.

Quality of Life and GEE Means and Standard Errors^a

	Baseline	Postintervention (8 Weeks)	6-Month Follow-Up	12-Month Follow-Up
IBDQ: total
Control	175.00 (6.34)	178.25 (7.90)	173.60 (8.19)	180.26 (4.25)
Mindfulness intervention	180.61 (4.75)	188.26 (3.55)	182.26 (5.60)	189.89 (4.25)
IBDQ: bowel symptoms
Control	5.74 (0.24)	5.96 (0.24)	5.66 (0.30)	5.90 (0.29)
Mindfulness intervention	5.98 (0.17)	6.21 (0.15)	6.01 (0.21)	6.18 (0.16)
IBDQ: emotional health
Control	5.36 (0.18)	5.34 (0.27)	5.26 (0.27)	5.55 (0.22)
Mindfulness intervention	5.47 (0.17)	5.74 (0.12)b	5.53 (0.23)	5.87 (0.13)b
IBDQ: systemic systems
Control	4.51 (0.17)	4.75 (0.22)	4.70 (0.23)	4.84 (0.16)b
Mindfulness intervention	4.76 (0.15)	4.93 (0.11)	4.86 (0.20)	4.95 (0.19)
IBDQ: social functioning
Control	6.26 (0.28)	6.34 (0.31)	6.21 (0.31)	6.22 (0.36)
Mindfulness intervention	6.36 (0.23)	6.55 (0.19)	6.42 (0.22)	6.71 (0.13)

All numbers reflect GEE estimate values. Abbreviations: GEE, generalized estimating equations; IBDQ, Inflammatory Bowel Disease Questionnaire.

P < 0.05.

Effects of MI on psychosocial outcomes, sleep, perceived stress, and stress biological response

We examined the impacts of the MI on psychosocial outcomes, including depression, anxiety, and sleep. Depression scores lowered over time in the MI group (Table 7), with significant reductions from baseline at 12 months (P = .03). Depression scores did not change significantly in the control group (all P values > .05). In the MI group, average anxiety scores were low at baseline (mean = 33.72) and remained low throughout the course of the follow-up, with no significant changes in either the MI or the control groups (all P values > .05).

Table 7.

Psychosocial Outcomes GEE Means and Standard Errors^a

	Baseline	Postintervention (8 Weeks)	6-Month Follow-Up	12-Month Follow-Up
Anxiety: STAI
Control	32.50 (2.15)	31.60 (2.57)	33.92 (3.06)	31.32 (2.28)
Mindfulness intervention	33.72 (2.79)	33.55 (2.70)	33.74 (2.69)	34.55 (2.69)
Depression: BDI
Control	9.70 (1.78)	7.81 (2.05)	9.76 (1.98)	6.87 (1.81)
Mindfulness intervention	6.56 (1.48)	4.79 (1.09)	5.10 (1.09)	3.60 (0.99)b
Sleep quality: PSQI
Control	7.40 (0.84)	6.95 (0.84)	6.59 (0.83)	6.52 (0.96)
Mindfulness intervention	5.94 (0.57)	4.82 (0.40)b	5.96 (0.69)	5.26 (0.80)
Perceived stress: PSQ
Control	0.39 (0.04)	0.34 (0.04)	0.40 (0.06)	0.33 (0.04)b
Mindfulness intervention	0.41 (0.04)	0.33 (0.04)b	0.34 (0.04)b	0.35 (0.04)b
Urinary cortisol
Control	57.92 (6.58)	55.32 (7.74)	57.21 (8.08)	58.67 (9.07)
Mindfulness intervention	49.93 (7.48)	44.86 (6.79)	44.66 (7.81)	35.02 (6.58)b

All numbers reflect GEE estimate values. Abbreviations: BDI, Beck Depression Inventory; GEE, generalized estimating equations; PSQ, Perceived Stress Questionnaire; PSQI, Pittsburgh Sleep Quality Index; STAI, State-Trait Anxiety Inventory.

P < .05.

The MI was associated with a significant improvement in sleep quality at the 8-week visit (P < .01) but returned to baseline levels at both the 6-month (P = .98) and 12-month (P = .35) visits. There were no significant changes in sleep quality in the control group, and there were no group-by-time interactions on any of the psychosocial outcomes.

We also analyzed the effects of the MI on perceived stress scores and stress reactivity (Table 7). In the MI group, perceived stress (PSQ) decreased significantly compared to baseline at the 8-week (P < .01), 6-month (P < .01), and 12-month (P = 0.02) visits. There were no significant group-by-time interactions in perceived stress at any time point. These results indicate that perceived stress was decreased in the MI group in both the short and long terms.

We also analyzed the effects of MI on the biological response to stress by measuring urinary cortisol. In the MI group, cortisol levels were significantly decreased at 12 months (P = .01) but were not significant at the other time points examined. There were no significant changes over time in the control group, and there were no significant group-by-time interactions in cortisol at any time point. These results suggest that the MI successfully blunted the host biological response to stress and stress reactivity, and the effect was long lasting even after 8 weeks of MI courses.

Discussion

Several studies have demonstrated that stress might be a trigger for UC flares in patients with IBD, and psychological stress has been shown to negatively impact the disease course.^3–6,34 Thus, we hypothesized that an effective stress-reducing intervention could decrease the frequency of UC flares. Mindfulness interventions, such as MBSR, have been shown to be an effective means to minimize perceived stress and the stress response by increasing the state of mindfulness and mindfulness skills.^11–16,35 Indeed, several studies have demonstrated positive impacts of MIs for stress-associated disorders and psychological disorders and for improving quality of life.^11–16 Ulcerative colitis is a chronic, inflammatory disorder, in which psychological stress has been shown to impact the disease course. Thus, it is highly plausible that interventions, such as an MI, could be effective in improving the disease course by decreasing stress.

In this trial, we sought to determine whether an MI will decrease perceived stress and responses to stress in UC patients by increasing the state of mindfulness and mindfulness skills and, if so, whether MI positively impacts the UC disease course by decreasing the frequency of UC flares. We found that MI increased the state of mindfulness and mindfulness skills, and decreased perceived stress and stress responses in patients with inactive UC. The MI also significantly decreased the frequency of UC flares and improved quality of life over the 12-month study period. None of the UC patients in the MI group flared during 12-month study, while 5 of 23 participants in the control group flared during the same period.

One potential mechanism for effectiveness of MI to improve the UC disease course is to improve the host response to stress. Indeed, we found that UC patients who were randomized to receive an 8-week MI had significantly lower perceived stress and lower 24-hour urinary cortisol after the MI, while perceived stress scores and urinary cortisol levels did not significantly change in those UC patients randomized to an 8-week time or attention intervention. The concept that increased mindfulness can decrease stress responses is supported by a prior study.³⁵ Our data suggest that the decreased host response to stress by MI might be the mechanism for the positive outcome of the intervention. We hypothesized that MI improves the UC disease course by mitigating the host response to stress, with a resulting decrease in inflammation. However, we did not find that the MI significantly affected intestinal or systemic inflammation markers (i.e., calprotectin, IL-6, IL-8), despite decreasing perceived stress (PSQ). Furthermore, there were no significant correlations between perceived stress (PSQ), urinary cortisol, stool calprotectin, nor serum cytokines. It is possible that the small sample size limited our ability to detect subtle changes in subclinical inflammation that were sufficient to prevent the sustained inflammatory cascades required to trigger a UC flare. Another possibility is that analysis of other pro- and anti-inflammatory markers (e.g., IL-10) may have revealed significant effects, and future studies should evaluate these alternative mechanisms.

Another possible mechanism for the positive outcome of the MI is in improved sleep quality. Studies have shown that IBD patients (even when in remission) have poor sleep quality, and those patients with poor sleep have a higher risk of flare.^36–39 Prior studies have shown that MI can improve sleep quality.^40–42 Indeed, we found that MI significantly improved sleep. However, the improvement was short lived and was only noted after the 8-week course of the intervention. Nonetheless, even short-lived improved sleep quality could potentially be restorative and minimize the deleterious impacts of chronic poor sleep on the UC disease course. It is possible that sustained improvements in sleep might require longer and/or repeated courses of mindfulness meditation. Notably, although multiple meta-analyses of the effect of MI on sleep quality have found significant improvement postintervention, the follow-up periods are typically between 3 and 5 months.^40,41

The positive effect on UC flare in this study is in contrast with our prior study, where the MI (MBSR) did not significantly decrease UC flares.¹⁷ The primary difference between these studies is the state of mindfulness at baseline. Participants in the prior study had high mindfulness scores and low levels of stress at baseline, and the MI did not significantly improve that mindfulness or perceived stress (ceiling effect; ¹⁷). In contrast, participants in the current study had a high level of perceived stress at baseline, which was significantly reduced by the MI. Based on this information, it should not be a surprise that the MI did not positively impact the UC disease course in our prior study, since our hypothesis is that MI improves the UC disease course by increasing mindfulness and decreasing stress. Similar to our prior study, we also showed that the MI significantly improved the quality of life in those with IBD, which was largely driven by the IBDQ emotional health scale. This finding is compatible with the positive impact of MI on several psychological aspects of UC patients, like significant improvements in depression symptoms. Our findings support prior studies showing that a poor quality of life in IBD patients is heavily influenced by their state of mind and the emotional aspects of IBD.^43–45 This adds to evidence that improved coping, through a MI, may positively impact our IBD patients’ quality of life.

The strengths of this study are the randomized, double-blind, controlled study design with 12 months of follow-up, longitudinal data and sample collection, and the use of multiple biological measures combined with psychological self-report measures. The primary limitation of this study is the relatively small sample size, due to difficulty in recruitment, suggesting that our analyses may have been underpowered. Future studies with larger sample sizes would allow for more detailed analyses of the relationships among the study variables.

In summary, we found that an 8-week MI significantly reduced UC flares and improved quality of life in patients with inactive UC and a high level of perceived stress at baseline. Specifically, the MI could improve the state of mindfulness, resulting in improved coping and decreased stress, which has been shown to trigger IBD flares.³⁴ Indeed, this conclusion is supported by prior studies that suggest stress is a trigger for UC flares.^3–6

Additional studies with larger sample sizes are needed to confirm the findings in this study. Finally, studies including active UC participants are required to determine the utility of MI across all UC patients. Our study is still 1 of a few reports that demonstrated that increases in the state of mindfulness and mindfulness skills can be a useful adjuvant therapy. Our findings suggest that MI could be considered as an adjuvant treatment for a subset of UC patients with high perceived stress and a low state of mindfulness.

Appendix 1. Measures

The Mayo Endoscopy Index

• 0 = Normal mucosal pattern

• 1 = Mucosal erythema, slight edema, red spots

• 2 = Superficial erosions, friable mucosa with bleeding upon touch, minimum spontaneous bleeding

• 3 = Marked spontaneous bleeding, severe mucosal ulcerations, large amounts of mucopurulent discharge

The Mayo Score Disease Activity Index for Ulcerative Colitis

Stool frequency

• 0 = Normal number of stools

• 1 = 1–2 stools more than normal

• 2 = 3–4 stools more than normal

• 3 = 5 or more stools more than normal

Rectal bleeding

• 0 = No blood seen

• 1 = Streaks of blood with stool less than half the time

• 2 = Obvious blood with stool most of the time

• 3 = Blood alone passes

Findings on endoscopy

• 0 = Normal or inactive disease

• 1 = Mild disease (erythema, decreases in vascular pattern, mild friability)

• 2 = Moderate disease (marked friability, erosions)

• 3 = Severe disease (spontaneous bleeding, ulceration)

Physician’s global assessment

• 0 = Normal

• 1 = Mild disease

• 2 = Moderate disease

• 3 = Severe disease

Modified Ulcerative Colitis Disease Activity Index

Please complete each evening before going to bed, starting 7 days before your next visit. Your answers should describe the preceding 24 hours.

Inflammatory Bowel Disease Quality of Life Questionnaire

Directions: This questionnaire is designed to find out how you have been feeling during the last 2 weeks. You will be asked about symptoms you have been having as a result of your inflammatory bowel disease, the way you have been feeling in general, and how your mood has been. PLEASE DO NOT SKIP any questions.

1. How frequent have your bowel movements been during the last two weeks? Please indicate how frequent your bowel movements have been during the last two weeks by picking one of the options from

   • 1 Bowel movements are more frequent than they have ever been

   • 2 Extremely frequent

   • 3 Very frequent

   • 4 Moderate increase in frequency of bowel movements

   • 5 Some increase in frequency of bowel movements

   • 6 Slight increase in frequency of bowel movements

   • 7 Normal., no increase in frequency of bowel movements

2. How often has the feeling of fatigue or of being tired and worn out been a problem for you during the last 2 weeks? Please indicate how often the feeling of fatigue or tiredness has been a problem for you during the last 2 weeks by picking one of the options from

   • 1 All of the time

   • 2 Most of the time

   • 3 A good bit of the time

   • 4 Some of the time

   • 5 A little of the time

   • 6 Hardly any of the time

   • 7 None of the time

3. How often during the last 2 weeks have you felt frustrated, impatient, or restless? Please choose an option from

   • 1 All of the time

   • 2 Most of the time

   • 3 A good bit of the time

   • 4 Some of the time

   • 5 A little of the time

   • 6 Hardly any of the time

   • 7 None of the time

4. How often during the last 2 weeks have you been unable to attend school or work because of your bowel problem? Please choose an option from

   • 1 All of the time

   • 2 Most of the time

   • 3 A good bit of the time

   • 4 Some of the time

   • 5 A little of the time

   • 6 Hardly any of the time

   • 7 None of the time

5. How much of the time in the last 2 weeks have your bowel movements been loose? Please choose an option from

   • 1 All of the time

   • 2 Most of the time

   • 3 A good bit of the time

   • 4 Some of the time

   • 5 A little of the time

   • 6 Hardly any of the time

   • 7 None of the time

6. How much energy have you had during the last 2 weeks? Please choose an option from

   • 1 All of the time

   • 2 Most of the time

   • 3 A good bit of the time

   • 4 Some of the time

   • 5 A little of the time

   • 6 Hardly any of the time

   • 7 None of the time

7. How often during the last 2 weeks did you feel worried about the possibility of needing to have surgery because of your bowel problem? Please choose an option from

   • 1 All of the time

   • 2 Most of the time

   • 3 A good bit of the time

   • 4 Some of the time

   • 5 A little of the time

   • 6 Hardly any of the time

   • 7 None of the time

8. How often during the last 2 weeks have you had to delay or cancel a social engagement because of your bowel problem? Please choose an option from

   • 1 All of the time

   • 2 Most of the time

   • 3 A good bit of the time

   • 4 Some of the time

   • 5 A little of the time

   • 6 Hardly any of the time

   • 7 None of the time

9. How often during the last 2 weeks have you been troubled by cramps in your abdomen? Please choose an option from

   • 1 All of the time

   • 2 Most of the time

   • 3 A good bit of the time

   • 4 Some of the time

   • 5 A little of the time

   • 6 Hardly any of the time

   • 7 None of the time

10. How often during the last 2 weeks have you felt generally unwell? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

11. How often during the last 2 weeks have you been troubled because of fear not finding a washroom (bathroom, toilet)? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

12. How much difficulty have you had, as a result of your bowel problems, doing leisure or sports activities you would have liked to have done during the last 2 weeks? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

13. How often during the last 2 weeks have you been troubled by pain in the abdomen? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

14. How often during the last 2 weeks have you had problems getting a good night’s sleep, or been troubled by waking up during the night? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

15. How often during the last 2 weeks have you felt depressed or discouraged? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

16. How often during the last 2 weeks have you had to avoid attending an event where there was no washroom (bathroom, toilet) close at hand? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

17. Overall, the last 2 weeks, how much of a problem have you had passing large amount of gas? Please choose an option from

    • 1 A major problem

    • 2 A big problem

    • 3 A significant problem

    • 4 Some trouble

    • 5 A little trouble

    • 6 Hardly any trouble

    • 7 No trouble

18. Overall, the last 2 weeks, how much of a problem have you had maintaining, or getting to the weight you would like to be at? Please choose an option from

    • 1 A major problem

    • 2 A big problem

    • 3 A significant problem

    • 4 Some trouble

    • 5 A little trouble

    • 6 Hardly any trouble

    • 7 No trouble

19. Many patients with bowel problems often have worries and anxieties related to their illness. These include worries about getting cancer, worries about never feeling better, and worries about having a relapse. In general, how often during the last 2 weeks have you felt worried or anxious? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

20. How much of the time during the last 2 weeks have you been troubled by a feeling of abdominal bloating? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

21. How often during the last 2 weeks have you felt relaxed and free from tension? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

22. How much of the time during the last 2 weeks have you had a problem with rectal bleeding with your bowel movements? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

23. How much of the time during the last 2 weeks have you felt embarrassed as a result of your bowel problem? Please choose an option

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

24. How much of the time during the last 2 weeks have you been troubled by a feeling of having to go to the bathroom (toilet) even though your bowels are empty? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

25. How much of the time during the last 2 weeks have you felt tearful or upset? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

26. How much o the time during the last 2 weeks have you been troubled by an accidental soiling of your underpants? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

27. How much of the time during the last 2 weeks have you felt angry as a result of your bowel problem? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

28. To what extent has your bowel problem limited sexual activity during the last 2 weeks? Please choose an option from

    • 1 No sex as a result of bowel disease

    • 2 Major limitation as a result of bowel disease

    • 3 Moderate limitation as a result of bowel disease

    • 4 Some limitation as a result of bowel disease

    • 5 A little limitation as a result of bowel disease

    • 6 Hardly any limitation as a result of bowel disease

    • 7 No limitation as a result of bowel disease

29. How much of the time during the last 2 weeks have you been troubled by nausea or feeling sick to your stomach? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

30. How much of the time during the last 2 weeks have you felt irritable? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

31. How often during the last 2 weeks have you felt a lack of understanding from others? Please choose an option from

    • 1 All of the time

    • 2 Most of the time

    • 3 A good bit of the time

    • 4 Some of the time

    • 5 A little of the time

    • 6 Hardly any of the time

    • 7 None of the time

32. How satisfied, happy, or pleased have you been with your personal life during the last 2 weeks? Please choose one of the following options from

    • 1 Very dissatisfied, unhappy most of the time

    • 2 Generally dissatisfied, unhappy

    • 3 Somewhat dissatisfied, unhappy

    • 4 Generally satisfied, pleased

    • 5 Satisfied most of the time, happy

    • 6 Very satisfied, most of the time,

    • 7 Extremely satisfied, could not have been more happy or pleased

3. Perceived Stress Questionnaire

Please answer these questions regarding how you feel within the past 4 weeks.

	Almost Never	Sometimes	Often	Usually
1. You feel rested	1	2	3	4
2. You feel that too many demands are being made on you	1	2	3	4
3. You are irritable or grouchy	1	2	3	4
4. You have too many things to do	1	2	3	4
5. You feel lonely or isolated	1	2	3	4
6. You find yourself in situations of conflict	1	2	3	4
7. You feel you’re doing things you really like	1	2	3	4
8. You feel tired	1	2	3	4
9. You fear you may not manage to attain your goals	1	2	3	4
10. You feel calm	1	2	3	4
11. You have too many decisions to make	1	2	3	4
12. You feel frustrated	1	2	3	4
13. You are full of energy	1	2	3	4
14. You feel tense	1	2	3	4
15. Your problems seem to be piling up	1	2	3	4
16. You feel you’re in a hurry	1	2	3	4
17. You feel safe and protected	1	2	3	4
18. You have many worries	1	2	3	4
19. You are under pressure from other people	1	2	3	4
20. You feel discouraged	1	2	3	4
21. You enjoy yourself	1	2	3	4
22. You are afraid for the future	1	2	3	4
23. You feel you’re doing things because you have to not because you want to	1	2	3	4
24. You feel criticized or judged	1	2	3	4
25. You are lighthearted	1	2	3	4
26. You feel mentally exhausted	1	2	3	4
27. You have trouble relaxing	1	2	3	4
28. You feel loaded down with responsibility	1	2	3	4
29. You have enough time for yourself	1	2	3	4
30. You feel under pressure from deadlines	1	2	3	4

5-Facet Mindfulness Questionnaire

Description

Please rate each of the following statements using the scale provided. Write the number in the blank that best describes your own opinion of what is generally true for you.

• 1 = Never/very rarely

• 2 = Rarely true

• 3 = Sometimes true

• 4 = Often true

• 5 = Very often/ always true

• _____ 1. When I’m walking, I deliberately notice the sensations of my body moving.

• _____ 2. I’m good at finding words to describe my feelings.

• _____ 3. I criticize myself for having irrational or inappropriate emotions.

• _____ 4. I perceive my feelings and emotions without having to react to them.

• _____ 5. When I do things, my mind wanders off and I’m easily distracted.

• _____ 6. When I take a shower or bath, I stay alert to the sensations of water on my body.

• _____ 7. I can easily put my beliefs, opinions, and expectations into words.

• _____ 8. I don’t pay attention to what I’m doing because I’m daydreaming, worrying, or otherwise distracted.

• _____ 9. I watch my feelings without getting lost in them.

• _____ 10. I tell myself I shouldn’t be feeling the way I’m feeling.

• _____ 11. I notice how foods and drinks affect my thoughts, bodily sensations, and emotions.

• _____ 12. It’s hard for me to find the words to describe what I’m thinking.

• _____ 13. I am easily distracted.

• _____ 14. I believe some of my thoughts are abnormal or bad and I shouldn’t think that way.

• _____ 15. I pay attention to sensations, such as the wind in my hair or sun on my face.

• _____ 16. I have trouble thinking of the right words to express how I feel about things

• _____ 17. I make judgments about whether my thoughts are good or bad.

• _____ 18. I find it difficult to stay focused on what’s happening in the present.

• _____ 19. When I have distressing thoughts or images, I “step back” and am aware of the thought or image without getting taken over by it.

• _____ 20. I pay attention to sounds, such as clocks ticking, birds chirping, or cars passing.

• _____ 21. In difficult situations, I can pause without immediately reacting.

• _____ 22. When I have a sensation in my body, it’s difficult for me to describe it because I can’t find the right words.

• _____ 23. It seems I am “running on automatic” without much awareness of what I’m doing.

• _____24. When I have distressing thoughts or images, I feel calm soon after.

• _____ 25. I tell myself that I shouldn’t be thinking the way I’m thinking.

• _____ 26. I notice the smells and aromas of things.

• _____ 27. Even when I’m feeling terribly upset, I can find a way to put it into words.

• _____ 28. I rush through activities without being really attentive to them.

• _____ 29. When I have distressing thoughts or images, I am able just to notice them without reacting.

• _____ 30. I think some of my emotions are bad or inappropriate and I shouldn’t feel them.

• _____ 31. I notice visual elements in art or nature, such as colors, shapes, textures, or patterns of light and shadow.

• _____ 32. My natural tendency is to put my experiences into words.

• _____ 33. When I have distressing thoughts or images, I just notice them and let them go.

• _____ 34. I do jobs or tasks automatically without being aware of what I’m doing.

• _____ 35. When I have distressing thoughts or images, I judge myself as good or bad,

• depending on what the thought/image is about.

• _____ 36. I pay attention to how my emotions affect my thoughts and behavior.

• _____ 37. I can usually describe how I feel at the moment in considerable detail.

• _____ 38. I find myself doing things without paying attention.

• _____ 39. I disapprove of myself when I have irrational ideas.

4. Beck Depression Inventory

Choose 1 statement from among the group of 4 statements in each question that best describes how you have been feeling during the past few days. Circle the number beside your choice.

1	0 I do not feel sad 1 I feel sad. 2 I am sad all the time and can’t snap out of it. 3 I am so sad or unhappy that I can’t stand it.	8	0 I don’t feel I am any worse than anybody else. 1 I am critical of myself for my weaknesses or mistakes. 2 I blame myself all the time for my faults. 3 I blame myself for everything bad that happens.
2	0 I am not particularly discouraged about the future. 1 I feel discouraged about the future. 2 I feel I have nothing to look forward to. 3 I feel that the future is hopeless and that things cannot improve.	9	0 I don’t have any thoughts of killing myself. 1 I have thoughts of killing myself, but I would not carry them out. 2 I would like to kill myself. 3 I would kill myself if I had the chance.
3	0 I do not feel like a failure. 1 I feel I have failed more than the average person. 2 As I look back on my life, all I can see is a lot of failure. 3 I feel I am a complete failure as a person.	10	0 I don’t cry any more than usual. 1 I cry more now than I used to. 2 I cry all the time now. 3 I used to be able to cry, but now I can’t cry even though I want to.
4	0 I get as much satisfaction out of things as I used to. 1 I don’t enjoy things the way I used to. 2 I don’t get any real satisfaction out of anything anymore. 3 I am dissatisfied or bored with everything.	11	0 I am no more irritated by things than I ever am. 1 I am slightly more irritated now than usual. 2 I am quite annoyed or irritated a good deal of the time. 3 I feel irritated all the time now.
5	0 I don’t feel particularly guilty. 1 I feel guilty a good part of the time. 2 I feel quite guilty most of the time. 3 I feel guilty all of the time.	12	0 I have not lost interest in other people. 1 I am less interested in other people than I used to be. 2 I have lost most of my interest in other people. 3 I have lost all of my interest in other people.
6	0 I don’t feel I am being punished. 1 I feel I may be punished. 2 I expect to be punished. 3 I feel I am being punished.	13	0 I make decisions about as well as I ever could. 1 I put off making decisions more than I used to. 2 I have greater difficulty in making decisions than before. 3 I can’t make decisions at all anymore.
7	0 I don’t feel disappointed in myself. 1 I am disappointed in myself. 2 I am disgusted with myself. 3 I hate myself.	14	0 I don’t feel that I look any worse than I used to. 1 I am worried that I am looking old or unattractive. 2 I feel that there are permanent changes in my appearance. 3 I believe that I look ugly.
15	0 I can work about as well as before. 1 It takes an extra effort to get started at doing something. 2 I have to push myself very hard to do anything. 3 I can’t do any work at all.	18	0 I haven’t lost much weight, if any, lately. 1 I have lost more than 5 pounds. 2 I have lost more than 10 pounds. 3 I have lost more than 15 pounds. (Score 0 if you have been purposely trying to lose weight).
16	0 I can sleep as well as usual. 1 I don’t sleep as well as I used to. 2 I wake up 1–2 hours earlier than usual and find it hard to get back to sleep. 3 I wake up hours earlier than I used to and cannot get back to sleep.	20	0 I am no more worried about my health than usual. 1 I am worried about physical problems such as aches and pains, or upset stomach, or constipation. 2 I am very worried about physical problems, and it’s hard to think of much else. 3 I am so worried about my physical problems that I cannot think about anything else.
17	0 I don’t get more tired than usual. 1 I get tired more easily than I used to. 2 I get tired from doing almost anything. 3 I am too tired to do anything.	21	0 I have not noticed any recent change in my interest in sex. 1 I am less interested in sex than I used to be. 2 I am much less interested in sex now. 3 I have lost interest in sex completely.
18	0 My appetite is no worse than usual. 1 My appetite is not as good as it used to be. 2 My appetite is much worse now. 3 I have no appetite at all anymore.

State-Trait Anxiety Inventory

DIRECTIONS: A number of statements which people have used to describe themselves are given below. Read each statement and then blacken in the appropriate circle to the right of the statement to indicate how you feel right now, that is, at this moment. There are no right or wrong answers. Do not spend too much time on any 1 statement but give the answer which seems to describe your present feelings best.

	Not at All	Somewhat	Moderately So	Much So
1. I feel calm.	(1)	(2)	(3)	(4)
2. I feel secure.	(1)	(2)	(3)	(4)
3. I am tense.	(1)	(2)	(3)	(4)
4. I feel strained.	(1)	(2)	(3)	(4)
5. I feel at ease.	(1)	(2)	(3)	(4)
6. I feel upset.	(1)	(2)	(3)	(4)
7. I am presently worrying over possible misfortunes.	(1)	(2)	(3)	(4)
8. I feel satisfied.	(1)	(2)	(3)	(4)
9. I feel frightened.	(1)	(2)	(3)	(4)
10. I feel comfortable.	(1)	(2)	(3)	(4)
11. I feel self-confident.	(1)	(2)	(3)	(4)
12. I feel nervous.	(1)	(2)	(3)	(4)
13. I am jittery.	(1)	(2)	(3)	(4)
14. I feel indecisive.	(1)	(2)	(3)	(4)
15. I am relaxed.	(1)	(2)	(3)	(4)
16. I feel content.	(1)	(2)	(3)	(4)
17. I am worried.	(1)	(2)	(3)	(4)
18. I feel confused.	(1)	(2)	(3)	(4)
19. I feel steady.	(1)	(2)	(3)	(4)
20. I feel pleasant.	(1)	(2)	(3)	(4)

Pittsburgh Sleep Quality Index

INSTRUCTIONS:

The following questions relate to your usual sleep habits during the past month only. Your answers should indicate the most accurate reply for the majority of days and nights in the past month.

Please answer all questions.

• 1. During the past month, what time have you usually gone to bed at night?

• BED TIME ___________

• 2. During the past month, how long (in minutes) has it usually taken you to fall asleep each night?

• NUMBER OF MINUTES ___________

• 3. During the past month, what time have you usually gotten up in the morning?

• GETTING UP TIME ___________

• 4. During the past month, how many hours of actual sleep did you get at night? (This may be different than the number of hours you spent in bed.)

• HOURS OF SLEEP PER NIGHT ___________

For each of the remaining questions, check the 1 best response. Please answer all questions.

• 5. During the past month, how often have you had trouble sleeping because you …

• a) Cannot get to sleep within 30 minutes

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• b) Wake up in the middle of the night or early morning

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• c) Have to get up to use the bathroom

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• d) Cannot breathe comfortably

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• e) Cough or snore loudly

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• f) Feel too cold

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• g) Feel too hot

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• h) Had bad dreams

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• i) Have pain

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• j) Other reason(s), please describe_______________

• How often during the past month have you had trouble sleeping because of this?

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• 6. During the past month, how would you rate your sleep quality overall?

• Very good ___________

• Fairly good ___________

• Fairly bad ___________

• Very bad ___________

• 7. During the past month, how often have you taken medicine to help you sleep (prescribed or “over the counter”)?

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• 8. During the past month, how often have you had trouble staying awake while driving, eating meals, or engaging in social activity?

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• 9. During the past month, how much of a problem has it been for you to keep up enough enthusiasm to get things done?

• No problem at all __________

• Only a very slight problem __________

• Somewhat of a problem __________

• A very big problem __________

• 10. Do you have a bed partner or roommate?

• No bed partner or room mate __________

• Partner/roommate in other room __________

• Partner in same room, but not same bed __________

• Partner in same bed __________

• If you have a roommate or bed partner, ask him/her how often in the past month you have had …

• a) Loud snoring

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• b) Long pauses between breaths while asleep

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• c) Legs twitching or jerking while you sleep

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• d) Episodes of disorientation or confusion during sleep

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

• e) Other restlessness while you sleep; please describe__________________________________

• Not during the past month_____

• Less than once a week_____

• Once or twice a week_____

• Three or more times a week_____

Expectancy and Credibility Questionnaire (first and fourth visits only)

We would like you to indicate below how much you believe, right now, that the program you are participating in will help to reduce any symptoms and/or prevent flare-up of your Ulcerative Colitis. Belief usually has 2 aspects: 1) what one thinks will happen; and 2) what one feels will happen. Sometimes these are similar; sometimes they are different. Please answer the questions below. In the first set, answer in terms of what you think. In the second set, answer in terms of what you really and truly feel.

Set I

• 1. At this point, how logical does the program offered to you seem?

• 1 23456789

• Not at all logicalSomewhat logical Very logical

• 2. At this point, how successfully do you think this treatment will be in reducing your symptoms and/or preventing flare-up of Ulcerative Colitis?

• 1 23456789

• Not at all usefulSomewhat usefulVery useful

• 3. How confident would you be in recommending this treatment to a friend who experiences similar problems?

• 123456789

• Not at all confidentSomewhat confidentVery confident

• 4. By the end of the class, how much improvement in y our Ulcerative Colitis symptoms do you think will occur?

• 0% 10%20%30%40%50%60%70%80%90%100%

Set II

For this set, close your eyes for a few moments and try to identify what you really feel about the class and its likely success. Then answer the following questions.

• 1. At this point, how much do you really feel that the class will help you to reduce your and/or prevent flare-up of your Ulcerative Colitis symptoms?

• 1 23456789

Not at allSomewhatVery much

• 2. By the end of the therapy period, how much improvement in your Ulcerative Colitis symptoms do you really feel will occur?

0%10%20%30%40%50%60%70%80%90%100%

Appendix 2. Power Analysis

The power for adjusted analyses of primary predictors of interest was evaluated as a function of the risk of the outcome when all ancillary variables are set to their mean value, the predictor is set to the mean value, the proportion of variance in the predictor is explained by the ancillary variables, and the odds ratio of the outcome variable increases the predictor by an amount equal to 1 of its standard deviation. The range in probabilities of outcome variables can be anywhere from 20% for less likely events to 50% for more likely events, and we will provide power calculations over a wide range of probabilities. We believe that the amount of variation of our typical model ranges from about 20% to 50%. The table below represents the minimum odds ratio that can be detected with 80% power, which indicate sufficient power for the expected changes in the primary outcome.

Proportions	R² = 0.20	R² = 0.50
0.10	1.64	1.87
0.20	1.46	1.63
0.30	1.39	1.53
0.40	1.35	1.48
0.50	1.32	1.43

Appendix 3. Data below includes the 5 subjects who flared.

The effect of Mindfulness intervention (MI) / time/attention control on markers of inflammation and UC-DAI and sigmoidoscopy score

		Baseline	Post-intervention	6-month	12-month follow
Sigmoidoscopy score
	MI	0.30 (0.34)	0.08 (0.77)	0.20 (0.63)	0.33 (0.35)
	Control	0.43 (0.28)	0.27 (0.46)	0.48 (0.29)	0.30 (0.34)
Histology score
	MI	0.90 (0.28)	0.56 (0.27)	0.68 (0.27)	0.63 (0.23)
	Control	1.22 (0.24)	1.11 (0.21)	0.91 (0.35)	0.59 (0.25)*
Stool Calprotectin
	MI	277.43 (125.67)	291.25 (118.18)	286.46 (107.02)	351.10 (138.81)
	Control	342.34 (120.80)	323.64 (96.10)	304.47(109.77)	375.71 (144.08)
IL-6
	MI	1.97 (0.27)	2.09 (0.41)	2.06 (0.36)	2.39 (0.61)
	Control	2.54 (0.57)	2.15 (0.38)	2.11 (0.30)	2.11 (0.33)
IL-8
	MI	5.03 (1.06)	4.26 (0.47)	4.88 (0.67)	4.73 (0.68)
	Control	8.96 (3.58)	6.72 (2.15)	9.46 (3.41)	7.87 (2.43)
CRP
	MI	0.21 (0.21)	0.26 (0.33)	0.27 (0.22)	0.40 (0.32)
	Control	0.45 (0.36)	0.28 (0.13)	0.27 (0.18)	0.80 (0.57)
UCDAI
	MI	3.41 (0.69)	3.30 (0.60)	3.01 (0.58)	3.18 (0.59)
	Control	3.46 (0.46)	3.97 (0.90)	4.51 (0.99)	3.92 (1.19)
Urgency
	MI	0.48 (0.17)	0.40 (0.14)	0.37 (0.12)	0.45 (0.13)
	Control	0.50 (0.11)	0.57 (0.17)	0.70 (0.19)	0.40 (0.19)

Note: Data presented reflect Generalized Estimating Equations (GEE) values; Means and Standard Errors.

*P < .05, UCDAI = ulcerative colitis disease activity index.

Author Contributions

A.K. conceived the hypothesis and designed the study; assessed study participants; performed the sigmoidoscopy, data analysis, and data interpretation; and is the guarantor of the article. S. Jedel assisted in the study design; led time and attention classes, the data analysis, and the data interpretation; and wrote the first draft of the manuscript. M.M.H. assisted in the study design and led the mindfulness-based intervention classes, data analysis, and data interpretation. G.S. assisted in assessing study participants and performed the sigmoidoscopy, data analysis, and data interpretation. R.M.V. assisted in the study design, data analysis, and data interpretation. T.B. conducted all statistical analyses and data interpretation. A.G. recruited and assessed study participants, collected all data, and performed data interpretation. S. Jakate performed the histological analysis and data interpretation. S.R. performed all laboratory measures and data interpretation. S.H. assisted in the study design, psychological assessment of study participants, data analysis, and data interpretation. All authors contributed to preparation of the manuscript.

Funding

This study was supported by a grant from the National Complementary Center for Alternative Medicine of the National Institutes of Health (Grant number R01 AT007143-01) and a philanthropic gift from the Skylar family.

Conflicts of Interest

None declared.