Digital Therapeutic Combining Hypnosis and Diaphragmatic Breathing Intervention for Functional Abdominal Bloating: A Feasibility Study

Abstract

INTRODUCTION:

Abdominal bloating is a difficult symptom to treat. Hypnotherapy and diaphragmatic intervention have separately shown benefit on bloating in prior work but have not been united into a single intervention. We aimed to obtain data on the potential therapeutic impact of a novel audio-recorded bloating treatment for bloating integrating hypnosis and diaphragmatic breathing, with proposed synergistic effect.

METHODS:

Patients with nonorganic bowel disorders with predominant bloating symptoms completed a digitally delivered 7-session audio-recorded hypnotherapy program without clinician involvement. The intervention combined bloating-targeted hypnotic suggestions and guided diaphragmatic breathing delivered under hypnosis, and was supplemented with interval self-guided breathing exercises. Participants completed online REDCap assessments at baseline, midtreatment, at end of treatment, and 3-month follow-up, evaluating symptom severity, gastrointestinal symptom-specific anxiety, overall anxiety/depression, and quality of life. Outcomes were assessed in an intention-to-treat manner with repeated measures analysis of variances (ANOVAs) with Bonferroni-adjusted pairwise post hoc tests.

RESULTS:

Of 23 patients who started treatment, 22 (95.6%) completed follow-up. Bloating severity on Irritable Bowel Syndrome-Symptom Severity Scale and Patient Assessment of Upper Gastrointestinal Symptom Severity Index showed reduction in bloating with large effect sizes (Cohen d of ∼0.8) at the end of treatment, as did Visceral Sensitivity Index bloating-related anxiety. At the end of treatment, 16 patients (69.6%) were Irritable Bowel Syndrome-Symptom Severity Scale treatment responders (≥30% symptom reduction) on bloating and 17 (73.9%) on overall bowel symptom severity. Anxiety, depression, and quality-of-life scores were unchanged. Outcome measures were fully maintained at the 3-month follow-up.

DISCUSSION:

Results suggest the therapeutic utility of a new cost-effective self-administered bloating intervention. A randomized controlled trial is planned to confirm these therapeutic effects.

BACKGROUND

Chronic abdominal bloating and distension are common gastrointestinal complaints with prevalence of 19% for bloating and 9% for distension in a general US population (1). Prevalence of bloating is as high as 90% among patients with irritable bowel syndrome (IBS) (2). Up to 75% of patients without IBS rate their bloating symptoms as moderate to severe, and 50% report reduction in daily activity due to bloating (3). Functional abdominal bloating (FAB) is a Rome IV disorder of gut-brain interaction (DGBI) defined by a subjective symptom of recurrent abdominal pressure, fullness, or trapped gas with or without accompanying objective increase in abdominal girth. In FAB, the bloating experienced is not associated with predominant pain or change in bowel movements and patients do not meet criteria for other DGBIs (4). The management of bloating remains a big challenge and a research priority for patients with and without IBS.

Current management of bloating with documented efficacy includes interventions such as a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet (5) and rifaximin therapy (6). However, these interventions are limited by risk of micronutrition deficiencies and difficulties in implementation, cost, microbiome disruption, and potential for development of antibiotic resistance. Studies of the mechanisms behind bloating/distension includes increased gas in the gastrointestinal therapies system in certain patients, but in most, a paradoxic contraction of the diaphragm, termed abdominophrenic dyssynergia, has been identified as a driver for bloating symptoms and development of distension (7). Limited options are available for correction of this dyssynergia with the only validated technique using electromyography-guided feedback to control abdominothoracic muscular activity, which is not widely accessible (8). In clinical practice, diaphragmatic breathing training has been used to address this issue with limited validation (9). Even diaphragmatic breathing education remains a limited resource because of lack of behavioral therapists and clinician familiarity. Other nonpharmacologic, centrally directed therapies including cognitive behavioral therapy and gut-directed hypnotherapy (GDH) have been shown to improve global IBS symptoms including bloating with minimal to no adverse effect (10). GDH is thought to improve visceral hypersensitivity and central pain processing with theorized impact on vagal nerve regulation, which can improve motility and regulate gut immune function (11). Regulation of these components may improve the discomfort and accompanying distress in patients with FAB and other DGBIs.

Traditionally, hypnotherapy is delivered in a one-on-one provider to patient interaction, which limits scalability and accessibility because of limited numbers of trained providers and poor access to providers for patients in areas of limited healthcare access. Digital and mobile health solutions have a role to play in leveling the field in access to and use of novel therapies once only available within a provider's office (12). The market of digital therapeutics, or software-based programs grounded in evidence-based medical practices, continues to grow to support access and accessibility of healthcare services. Digitally delivered hypnotherapy has been shown to be effective in treatment of irritable bowel syndrome in prior studies and is currently available for patient use (13,14). However, empirical evidence to support adoption of new digital therapeutics, such as self-administered hypnotherapy for upper GI symptom indications, such as FAB, is currently limited (15). Therefore, this study presents the approach taken to develop, administer, and perform a small scale feasibility assessment (16) of self-administered hypnotherapy as a digital therapeutic for patients experiencing chronic abdominal bloating and distension to inform further efficacy evaluation in the future.

We developed a digitally delivered, self-guided hypnotherapy intervention for patients with chronic abdominal bloating. We conducted a pilot study of this intervention to obtain preliminary evidence of effectiveness.

METHODS

Hypnotherapy protocol

A hypnotherapy session occurs in 4 stages, with an initial “induction” stage to bring the patient into the hypnotic trance state; “deepening,” to further engage the patient in trance; “suggestions,” during which the therapeutic content is delivered, and “realerting,” which brings the patient out of trance and back into their normal cognitive state. Both the induction and deepening stages are performed using methods to help patients engage with their bodily function in a paced manner (counting, progressive muscle relaxation, and visualization). Among these techniques, diaphragmatic breathing has been used clinically as a tool to facilitate hypnotherapy sessions.

A self-administered hypnotherapy script was developed based on effective protocols for the treatment of disorders of gut-brain interaction (DGBI) including IBS, functional heartburn, and for maintenance of quiescence in ulcerative colitis (10). The protocol was developed by a gastroenterologist trained in hypnotherapy in collaboration with a doctorate-level psychologist with expertise and experience in both face-to-face and digital hypnotherapy. Diaphragmatic breathing was built directly into the hypnosis script and was used for both induction and deepening of the hypnotic state. Within the hypnotic state, hypnotic suggestions targeted bloating and overall visceral hypersensitivity. The final protocol consists of 7 audio-recorded sessions delivered through digital application (smartphone or computer) without clinician involvement over the course of 12 weeks in accordance with current gut-direct hypnotherapy practice. Hypnotherapy sessions were delivered to the patients every 2 weeks. Between sessions, an audio-recorded guided diaphragmatic breathing practice was recorded and provided for enhanced practice. Patients were encouraged to use the guided recording and transition to diaphragmatic breathing without guidance when they were comfortable.

Study protocol

Patients with nonorganic bowel disorders with predominant bloating symptoms were identified from clinical lists and physician referrals. Inclusion criteria included patients who met Rome IV criteria (17) for FAB/distension or if bloating was a predominant symptom of another Rome IV DGBI, including, but not limited to, IBS and functional dyspepsia. Patients with diagnosis of small intestinal bacterial overgrowth, gastroparesis, pelvic floor dysfunction, rumination syndrome, and inflammatory bowel disease were excluded.

Patients underwent telehealth visits with a study physician to review history, evaluate for exclusion criteria, and for education on hypnotherapy and review of the study procedures. Patients were provided a prerecorded video explaining the concepts of hypnotherapy and the trial protocol. Eligibility questionnaires were administered, including the abridged bowel disease questionnaire and hospital anxiety and depression questionnaire (HAD) (18,19). To qualify, patients had to have symptoms of bloating on ABDQ.

Patient-reported outcomes

Eligible patients completed baseline symptom, mood, and quality of life (QoL) questionnaires.

The IBS-Symptom Severity Scale (IBS-SSS) is a 5-item assessment of IBS symptom severity using a scale of 0–100 to grade each symptom with higher scores, indicating greater severity or impact. The final score is a summation of the 5 individual components and is interpreted as inactive/no IBS (0–75), mild (75–175), moderate (175–300), or severe (>300) (20) (Figures 1 and 2).

Figure 1.

Changes in mean bloating severity over the treatment course and at the 3-month follow-up, on the 2 bloating measures used in the study. Intention-to-treat analysis; N = 23. Error bars = standard error. IBS-SSS, Irritable Bowel Syndrome-Symptom Severity Scale; PAGI-SYM, Patient Assessment of Upper Gastrointestinal Symptom Severity Index.

Figure 2.

Changes in IBS-SSS and bloating measures by baseline symptom severity. IBS-SSS, Irritable Bowel Syndrome-Symptom Severity Scale.

The Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) assesses symptom severity of upper GI symptoms and consists of 20 questions grouped in 6 subscales. Each symptom severity question is scored on a 6-point Likert response scale ranging from 0 (none) to 5 (very severe) based on a 2-week recall period. Each subscale is scored by taking the mean of the items within the scale with a total score calculated from the mean of the subscale scores (21).

The Visceral Sensitivity Index (VSI) is a 15-item questionnaire used to measure gastrointestinal-specific anxiety (fear, worry, and hypervigilance about symptoms and potential consequences). Each item is scored on a 6-point Likert scale ranging from 1 (strongly agree) to 6 (strongly disagree). The items are reverse scored so that 1 to 6 becomes 5-0 and then totaled with higher scores indicating more severe GI-specific anxiety (22).

The Hospital Anxiety and Depression Score (HADS) is designed to assess levels of anxiety and depression in patients in both hospital and clinical settings. The HADS consists of 14 items divided equally into anxiety and depression subscales. Each item is scored on a 4-point Likert scale ranging from 0 to 3 with higher numbers, indicating more severe symptoms. Each question is then summed for a total score on each subscale which is interpreted as normal (0–7), borderline abnormal (8–10), or abnormal (11–21) (19).

The EuroQol-5D (EQ-5D) is used to measure health-related QoL with 2 components capturing the day of assessment only. The EQ5D-5L comprises 5 items covering 5 dimensions of health with a 5-level response (no problems to unable to/extreme problems) that is then coded by each dimension. The second visual analog scale component assesses overall health on a 0 (worst)–100 (best) scale on that day (23).

Symptoms were assessed midway through the study with IBS-SSS and PAGI-SYM. At the end of study, and during the 3-month follow up, patients completed symptom assessment with IBS-SSS and PAGI-SYM as well as secondary outcomes assessment with EQ-5D, HAD, and VSI. All surveys were administered digitally by using REDCap.

The primary outcomes were change in bloating and overall symptom score measured using the validated IBS-SSS and the PAGI-SYM. A value of ≥30% reduction in bloating score was used as an exploratory outcome, given the US Food and Drug Administration cutoff of using >30% pain reduction as a marker of response. Secondary outcomes included the change in visceral sensitivity measured with the VSI and impact on overall health with the EQ-5D. Satisfaction with digital delivery platform was assessed using an end-of-treatment survey.

Statistical analysis

Outcomes were assessed in an intention-to-treat manner, with the last observation on each participant carried forward across time points, and repeated measures (one tailed ANOVAs) with Bonferroni-adjusted pairwise post hoc tests with a significance value set at P < 0.05. Cohen d effect sizes were calculated to aid interpretation of the practical meaningfulness of changes from baseline. Missing data were imputed. Subgroup analysis was undertaken stratifying patients by IBS-SSS severity. Single factor ANOVA test was performed for change in IBS-SSS total score comparing groups by baseline severity. The study was reviewed and approved by the Mayo Clinic IRB #22–003898.

RESULTS

A total of 35 patients underwent screening with 25 patients enrolled. Twenty-three of the 25 eligible patients started treatment and were included in the intention-to-treat analyses, and 22 (95.6%) completed treatment and follow-up. One patient was lost to follow-up before study initiation, and another was excluded due to minimal to no symptoms of bloating at the time of baseline assessment. Participants were predominantly female (n = 17, 77%), average age was 41 years (SD ± 14), and were predominantly White (n = 17, 77%) (Table 1). Eleven participants (50%) completed all 7 sessions, 8 completed 6 of 7 sessions, 2 completed 5 of 7 sessions, and one completed only 2 sessions. Patients were considered treatment completers if they completed most treatment sessions.

Table 1.

Demographic characteristics of participants enrolled in a digital intervention for functional abdominal bloating (N = 23)

	n = 23 (%)
Gender: female	17 (73.9%)
Age: yr, mean (SD)	40.7 (14.09)
Race
White	17 (73.9%)
Black or African American	1 (4.3%)
Asian	3 (13.0%)
Other	2 (8.7%)
Ethnicity
Hispanic or Latino	1 (3.9%)
Not Hispanic or Latino	14 (60.9%)
Declined to report	6 (26.1%)
Baseline IBS-SSS (n)
Mild (<175)	6
Moderate (175–275)	12
Severe (>275)	5
Baseline PAGI-SYM score, mean (SD)
Bloating	3.39 (0.19)
Total	1.68 (0.15)
Baseline HADS, n
Anxiety
≤7
8–10	15
≥11	3
Depression	4
≤7	20
8–10	2
≥11	0
Baseline total VSI, mean (SD)	34.3 (3.67)
IBS-SSS mild (<175)	27.3 (8.9)
IBS-SSS moderate (175–275)	32.9 (4.9)
IBS-SSS severe (>275)	41.4 (6.2)
Baseline bloating VSI subscore, mean (SD)	3.61 (0.28)
IBS-SSS mild (<175)	3.17 (0.48)
IBS-SSS moderate (175–275)	3.5 (0.54)
IBS-SSS severe (>275)	4.14 (0.26)
Baseline EQ-5D, mean (SD)	67.5 (3.38)
IBS-SSS mild (<175)	77.67 (3.53)a
IBS-SSS moderate (175–275)	70.5 (4.48)
IBS-SSS severe (>275)	54.4 (6.40)

EQ-5D, EuroQol-5D; HADS, Hospital Anxiety and Depression Score; IBS-SSS, Irritable Bowel Syndrome-Symptom Severity Scale; PAGI-SYM, Patient Assessment of Upper Gastrointestinal Symptom Severity Index; Qol, quality of life; VSI, Visceral Sensitivity Index.

^aP = 0.0187 on single factor analysis of variance.

Primary outcomes

At baseline, participants had an average IBS-SSS bloating score of 56.1 and total IBS-SSS score of 223. Most patients had moderate overall IBS-SSS symptoms (52.2%, n = 12), and 21.7% (n = 5) had severe symptoms. By the end of treatment, the bloating score had decreased to 31.3 (P = 0.003) with Cohen effect size of −0.84, which persisted at the 3-month follow-up (score of 32.3, P < 0.001, d = 0.96). Using a treatment response rate of ≥30% symptom reduction, 69.6% (n = 16) of patients were treatment responders on bloating and 73.9% (n = 17) were responders by overall symptom severity (IBS-SSS) (Table 2). By 3-month follow up, no patients had severe symptoms by IBS-SSS, 31.5% (7/23 responders) had moderate symptoms, and 69.6% (16/23) had mild symptoms, including 7 patients who had IBS-SSS scores <75.

Table 2.

Intention-to-treat outcomes of participants enrolled in a digital intervention for functional abdominal bloating (N = 23)

Outcome measure	Pretreatment	Midtreatmenta	End of treatment	3-mo follow-up
IBS-SSS bloating severity (primary outcome measure)	M = 56.1 ± 3.1	M = 40.4 ± 3.6 P = 0.020, d = −0.70	M = 31.3 ± 5.3 P = 0.003, d = −0.84	M = 32.3 ± 5.1 P < 0.001, d = −0.96
PAGI-SYM bloating severity	M = 3.39 ± 0.19	M = 2.61 ± 0.18 P = 0.002, d = −0.87	M = 2.09 ± 0.26 P = 0.001, d = −0.93	M = 2.17 ± 0.26 P = 0.002, d = −0.90
VSI bloating-specific anxiety	M = 4.57 ± 0.28	M = 3.48 ± 0.33 P = 0.002, d = −0.90	M = 2.96 ± 0.36 P = 0.006, d = −0.80	M = 2.87 ± 0.33 P < 0.001, d = −1.00
HADS anxiety	M = 6.17 ± 0.72	Not assessed	M = 6.52 ± 0.99 P = 1.000, d = 0.11	M = 5.96 ± 0.59 P = 1.000, d = −0.09
HADS depression	M = 2.93 ± 0.55	Not assessed	M = 3.13 ± 0.56 P = 1.000, d = 0.09	M = 3.44 ± 0.51 P = 0.760, d = 0.25
EuroQol EQ-5D	M = 66.5, SE = 3.5	M = 71.4 ± 3.3 P = 1.000, d = 0.28	M = 70.6 ± 2.8 P = 1.000, d = 0.26	M = 75.3 ± 2.2 P = 0.130, d = 0.52
IBS-SSS overall bowel symptom severity	M = 223.5 ± 18.7	M = 142.2 ± 17.3 P = 0.010, d = −0.95	M = 133.5 ± 16.1 P = 0.002, d = −0.89	M = 127.4 ± 15.9 P = 0.020, d = −0.87
PAGI-SYM total score	M = 1.70 ± 0.15	M = 1.30 ± 0.12 P = 0.040, d = −0.64	M = 1.04 ± 0.14 P < 0.001, d = −0.96	M = 1.03 ± 0.13 P = 0.002, d = −090
VSI total score	M = 34.3 ± 3.8	M = 29.1 ± 3.8 P = 0.270, d = −0.46	M = 19.4 ± 3.5 P = 0.020, d = −0.72	M = 19.7 ± 3.3 P < 0.001, d = −1.03

d = Cohen effect size of the difference compared with pretreatment values; EQ-5D, EuroQol-5D; HADS, Hospital Anxiety and Depression Score; IBS-SSS, Irritable Bowel Syndrome-Symptom Severity Scale; M, mean + standard error; P = Bonferroni-adjusted significance of change compared with baseline; PAGI-SYM, Patient Assessment of Upper Gastrointestinal Symptom Severity Index; Qol, quality of life; VSI, Visceral Sensitivity Index.

^aMidtreatment assessment was conducted between session 3 and 4 of the therapy program.

On the PAGI-SYM, participants had an average baseline score of 1.70, which improved to 1.04 (P < 0.001, d = −0.96) at the end of treatment and 1.03 (P = 0.020, d = −0.90) at the 3-month follow-up. The bloating domain had a baseline mean score of 3.39, which improved to 2.09 (P = 0.001, d = −0.93) at the end of treatment and 2.17 (P = 0.002, d = -0.9) at the 3-month follow-up. This meets the minimal clinical important difference of 0.3–0.7 points recommended for bloating scores as defined by the PAGI-SYM scale.

Secondary outcomes

Quality of life was evaluated by the EuroQol EQ5D and had a nonsignificant improvement from mean of 66.5 at baseline to 70.6 (P = 1.000) at the end of treatment and 75.3 at the 3-month follow-up (P = 0.130). 27.2% (n = 6) participants met criteria for anxiety by HADS at baseline, and none met criteria for depression. There was no significant change in anxiety or depression scores on HADS, with anxiety going from baseline of 6.17 to 5.96 at 3 months (P = 1.000), and depression from 2.93 to 3.44 (P = 0.760). Notably, at the 3-month follow-up, only 10% (3/20) of the respondents met criteria for anxiety. However, the disease-specific anxiety changed by VSI both in total score, changing from baseline of 34.3 to 19.4 at the end of treatment (P = 0.020) and 19.7 at 3 months (P < 0.001) and in bloating-specific anxiety on VSI, from a baseline of 4.57 to 2.96 at the end of treatment (P = 0.006) and 2.87 at 3 months (P < 0.001).

Subgroup analysis

Outcomes were evaluated by baseline IBS-SSS severity. At the end of treatment, participants with mild IBS-SSS scores experienced a mean 1.67 ± 67.9 point difference in IBS-SSS score compared with 101.7 ± 87.4 point improvement in those with moderate IBS and 212 ± 37.0 point improvement in those with severe symptoms (Table 3). This was statistically significant with P < 0.001 for between group variances. This was similar when assessing the 3-month follow-up with mean changes of 6.67, 131.67, and 212 points on the IBS-SSS score in the mild, moderate, and severe groups (P = 0.006).

Table 3.

Subgroup analysis by IBS severity

	Baseline	End of treatment	3 mo follow-up
IBS-SSS, n
Mild (<175)	6	16	13
Moderate (175–300)	12	5	6
Severe (>300)	5	1	0

	Baseline	Change at end of treatment	P value	Change at 3 mo follow-up	P value
IBS-SSS total score, mean (SD)			<0.001		0.006
IBS-SSS mild	110 (47.7)	1.67 (67.9)		6.7 (69.5)
IBS-SSS moderate	230.8 (37.8)	101.7 (87.4)		131.7 (95.7)
IBS-SSS severe	340 (28.3)	212.0 (37.0)		212.0 (121.1)
IBS-SSS bloating, mean (SD)			0.290		0.330
IBS-SSS mild	41.7 (14.7)	15.0 (38.5)		15.0 (32.1)
IBS-SSS moderate	61.7(11.9)	26.7 (26.4)		35.0 (23.2)
IBS-SSS severe	60.0 (12.2)	44.0 (23.0)		38.0 (37.7)
IBS-SSS bloating score, mean (SD)			0.005 a		0.008 a
Bloating mild (≤50)	40.0 (8.7)	5.6 (31.7)		12.2 (27.3)
Bloating severe (>50)	66.4 (6.3)	41.4 (18.8)		42.1 (24.6)
Total VSI, mean (SD)	34.3 (3.67)		0.990
IBS-SSS mild	27.3 (8.9)	15.2 (18.1)
IBS-SSS moderate	35.0 (4.4)	16.0 (24.7)
IBS-SSS severe	39.8 (8.4)	14.6 (14.3)
Bloating VSI subscore, mean (SD)	3.61 (0.28)		0.750
IBS-SSS mild	3.17 (0.48)	1.8 (1.8)
IBS-SSS moderate	3.67 (0.47)	1.4 (2.4)
IBS-SSS severe	4.00 (0.32)	2.2 (1.6)
EQ5D, mean (SD)	67.5 (3.38)		0.650		0.480
IBS-SSS mild	77.67 (3.5)	−5.0 (15.3)		2.3 (8.8)
IBS-SSS moderate	66.67 (5.0)	1.1 (26.1)		−8.3 (42.5)
IBS-SSS severe	57.20 (7.0)	8.0 (21.5)		12.8 (18.6)

EQ-5D, EuroQol-5D; IBS-SSS, Irritable Bowel Syndrome-Symptom Severity Scale; Qol, quality of life; VSI, Visceral Sensitivity Index.

^aPaired t-test with unequal variance; one-tail; IBS-SSS Mild (<175), IBS-SSS Moderate (175–300), IBS-SSS Severe (>300).

When change in bloating score was evaluated by baseline total IBS-SSS severity, no significant difference was found among the groups, with mean score changes of 15, 26.7, and 44 points in the mild, moderate, and severe groups at the end of treatment (P = 0.290). However, when groups were compared by baseline low (≤50) or high (>50) bloating subscores on the IBS-SSS, a significant difference in response was observed with an average of 12.22 points improvement in the low bloating group compared with 42 points in the high bloating group (P = 0.008) at the 3-month follow-up.

Anxiety by HADS did not change significantly when comparing across baseline IBS-SSS severity (P = 0.750). Quality of life at baseline decreased with increasing symptom severity with an average score of 77.7, 66.7, and 57.2 in the mild, moderate, and severe groups, respectively, but this was not statistically significant (P = 0.650). Quality of life at the 3-month follow-up improved more in those with severe baseline disease (mean change 12.8) compared with mild or moderate (2.33, −8, respectively), but this was not statistically significant (P = 0.480). Those with more severe disease at baseline did have higher average baseline VSI scores (Table 3), but this was not statistically significant for bloating (P = 0.980) or total VSI (P = 0.670). Improvement in GI symptom-specific anxiety also did not differ by baseline disease severity with an end-of-treatment change in total VSI score of 15.2, 16.0, and 14.6 in the mild, moderate, and severe groups (P = 0.980). This was similar when evaluating anxiety around bloating symptoms with average improvement of 1.8, 1.4, and 2.2 in the mild, moderate and severe groups (P = 0.750).

Patient experience and practice session compliance

Overall, 90.9% (20/22) of participants who completed the treatment reported satisfaction with the therapy with 10 being satisfied and 10 very satisfied (Figure 3).

Figure 3.

Patient-reported satisfaction.

Patients were encouraged at the beginning of the study to practice diaphragmatic breathing twice daily. At the end of trial, most patient reported practicing less than 5 times per week (n = 10, 45%), with 9 (40.1%) reporting practicing at least 5 times per week. Two patients (0.9%) practiced at least once per day, and one patient reported adhering to twice daily practice. Amount of practice did not correlate with changes in total IBS-SSS (P = 0.110) or bloating subscore (P = 0.310) nor did amount of practice correlate with changes in anxiety, symptom specific anxiety, or quality-of-life scores.

Adverse events

There were no adverse events attributable to the study.

DISCUSSION

Digitally delivered hypnotherapy has been shown to be helpful in various DGBIs including irritable bowel syndrome (14) and functional dyspepsia (24,25).

Our novel digital intervention integrated diaphragmatic breathing with hypnotherapy into a single, self-administered digital intervention. Diaphragmatic breathing was incorporated into each therapeutic session as an induction tool, deepening tool, or woven into the therapeutic suggestion. The frequency of interval diaphragmatic breathing practice was not associated with more symptom improvement, suggesting that diaphragmatic breathing alone is not responsible for the improvements seen.

Using this integrated protocol, most participants experienced significant symptom reduction in not only bloating but also in overall symptoms on both upper GI (PAGI-SYM) and lower GI (IBS-SSS) assessments with significant impacts. In line with previously studied protocols, these improvements were noted midway through treatment, but symptom scores continued to decline to the end of treatment with maintenance of effect at the 3-month follow-up, reiterating the importance of a complete treatment period.

Baseline symptom burden affected clinical response with participants with baseline severe IBS-SSS demonstrating the greatest response to hypnotherapy treatment. Similarly, those with higher bloating scores at baseline had greater response to treatment.

Despite improvement in symptoms, we did not observe statistically significant improvements in quality of life or changes in anxiety or depression scores, though the number of participants who met criteria for anxiety by HADS subscore did decrease. However, like other studies of gut-directed behavioral psychotherapies, we found significant improvement in disease and GI symptom-specific anxiety with decrease in VSI score specific to bloating and overall.

Symptom-specific anxiety scores were not significantly different among different IBS-SSS severity groups at baseline, and the degree of improvement also did not differ significantly between groups, despite an overall significant change. This would suggest that symptom severity alone does not determine the amount of distress a patient experiences around those symptoms.

Nearly, all patients reported a favorable experience with this digital therapeutic. This intervention is the first to integrate 2 behavioral modalities into a digital therapeutic system and showed positive benefit in this pilot and feasibility trial. This protocol has potential to be a safe and acceptable treatment mechanism for patients with bloating as a syndrome or as a primary component of treatment for other DGBIs.

Our study is limited by a small sample size and lack of a control arm, which limits our ability to examine the specificity of the treatment effect vs placebo response or to robustly evaluate the proposed synergy between diaphragmatic breathing and hypnotherapy. The reported placebo response rate in literature for IBS-SSS has been reported as high as 70%, but with modest effect sizes (d = 0.46) at best (26) but ranges around 10%–30% in drug trials (27,28) and 27%–35% in prior studies of digital GDH for IBS (13,14). Despite our small sample size, we were able to observe significant improvement in not only bloating symptoms but overall symptoms of upper and lower DGBIs with 73.9% of patients seeing improvement in IBS-SSS with a large effect size, suggesting possibility of treatment effect. The trial combines hypnotherapy and diaphragmatic breathing technique without the ability to discern which technique is influencing symptom improvement. However, the intention of the protocol is to combine and augment these 2 techniques. It is unlikely that diaphragmatic breathing alone is responsible for the full impact in this study as there are no differences in symptom changes based on how frequently diaphragmatic breathing practice was performed between hypnosis sessions. Further studies are currently under development to validate this protocol against control and further understand its underlying pathophysiology and develop prognosticating tools to predict likelihood of response.

CONCLUSIONS

The findings of this pilot and feasibility study of a novel, digitally delivered, clinician-independent protocol-integrating hypnotherapy and diaphragmatic breathing are encouraging as evidenced by large bloating reduction in most patients, improvement in overall GI symptoms, and gut-focused anxiety after treatment. Patients with higher symptom burden at baseline had greater symptom improvements, but symptom burden at baseline did not predict improvement in gut symptom-focused anxiety. Therapeutic impact was maintained at the 3-month follow-up. Future directions include validation trials and identifying the ideal patients who would benefit from this intervention.

CONFLICTS OF INTEREST

Guarantor of the article: Xiao Jing Wang, MD.

Specific author contributions: X.J.W. and O.P. conceived and developed the treatment protocol. X.J.W., C.L., F.J., and O.P. developed the initial study plan which was reviewed with input from L.P. and J.E. S.D. contributed to study development and data collection. X.J.W. drafted the initial manuscript. All authors provided critical feedback and helped shape the research, analysis and manuscript.

Financial support: Funding was provided by an internal grant provided by the Mayo Clinic Division of Gastroenterology and Hepatology.

Potential competing interests: Copyright and intellectual property for the hypnotherapy protocol is owned by Mayo Clinic. The authors have no competing interests and no financial disclosures relevant to this study.

ClinicalTrial.gov ID: NCT05572606.

Study Highlights.

WHAT IS KNOWN

• ✓ Functional abdominal bloating alone or as part of another disorder of gut-brain interaction (DGBI) is a common problem affecting up to 1 in 5 individuals in a general US population

• ✓ Treatment options for functional abdominal bloating or bloating as part of a DGBI is limited in number and those available can be limited by side effects or cost.

• ✓ Brain-gut-directed therapies, including hypnotherapy, have been used successfully in the treatment of other DGBIs.

• ✓ Diaphragmatic breathing intervention can be helpful for abdominophrenic dyssynergia, which can contribute to bloating and distension.

WHAT IS NEW HERE

• ✓ We developed a new protocol, embedding diaphragmatic breathing as part of a self-directed hypnotherapy delivered digitally without clinician involvement.

• ✓ Digitally delivered therapy was well accepted with high adherence and completion rates.

• ✓ Over two-thirds of patients saw improvement in their bloating symptoms and overall DGBI symptomatology with greater improvements in those with higher initial disease burdens.