Benefits From and Barriers to Portable Detection of Gluten, Based on a Randomized Pilot Trial of Patients with Celiac Disease

INTRODUCTION

Research links diminished quality of life (QOL) to the challenges of a strict gluten-free diet (GFD), the only treatment for celiac disease (CD) [1–4]. This pilot study assessed the acceptability and feasibility of a portable gluten sensor device (“Nima”) to promote GFD adherence and QOL.

A prior validation study found that Nima reliably indicates “gluten found” in gluten-free foods having ≥ 20 ppm added gluten (92.6% of samples tested) [5]. With 5 – 19 ppm of gluten added (considered gluten-free by the U.S. FDA [6]), specificity varies: “gluten found” 34.6% of the time with 5 ppm added, 56.4% of the time with 10 ppm [5,7].

Methods

This study was conducted at a CD Center in New York City (IRB#AAAR6004; authors had data access and approved manuscript). Eligibility was assessed by telephone and required biopsy-confirmed diagnosis, treatment at Center, no current Nima, and owning an iPhone 5+.

Enrollment occurred February-April 2018. Target goal was 15 adults (≥18 years) and 15 teenagers. Recruitment was via flyers and emails to tri-state affiliates. Five each of adults and teenagers were enrolled and randomized to receive 24, 12 or 6 single-use testing capsules per month. Researchers demonstrated the use of the device but offered no recommendations for what, where, or when to test. Manufacturer’s handouts described how to pair the device with the app, how to run a test, and what can/cannot be accurately tested.

Outcomes, collected at baseline and three-month follow-up, included validated measures of CD-specific QOL, GFD adherence, depression and anxiety. Closed-format items included 17 benefits, nine barriers, four plans for continued use, and overall recommendation. We also asked about satisfaction with capsule supply and administered a quiz regarding the device’s capability of accurately testing specific foods.

Results

Two-thirds (67%) of participants were female. All but one self-identified as white, non-Hispanic. Mean age of adults was 38.6 years (SD = 16.5); of teenagers, 15.5 (SD = 1.6). All but two adults were college graduates.

At follow-up, adults reported improved Overall and Limitations CD-specific QOL and depression scores (Table 1). Teenagers exhibited no changes. Six participants, all randomized to the lower use groups, desired more capsules. Adults and teenagers displayed a similar understanding of the device’s testing limitations (mean 4.5 of six foods correct).

Table 1:

Quality of Life, Adherence, Depression, Anxiety and GI symptoms before and after NIMA intervention

	Adults
	Pre-	Post-	Paired t-test5
	Mean (SD)	Mean (SD)	t	p
Overall Quality of Life (CD-QOL)1	45.7 (22.6)	54.5 (22.6)	−3.4	0.005
Dysphoria subscale1	66.7 (25.7)	72.1 (25.8)	−1.7	0.12
Limitations subscale1	37.2 (24.8)	48.8 (26.1)	−3.7	0.002
Health Concerns subscale1	45.7 (27.8)	53.3 (23.7)	−1.7	0.12
Inadequate treatment subscale1	42.5 (32.7)	47.5 (36.7)	−1.1	0.29
GF-diet Adherence (CDAT)2	11.1 (1.5)	10.8 (2.1)	0.6	0.58
Depression (CESD)3	15.3 (9.2)	11.3 (9.5)	2.4	0.03
Anxiety State (STAI Adults)4	63.1 (13.6)	61.4 (11.4)	0.4	0.70
Anxiety Trait (STAI Adults)4	57.4 (12.4)	57.5 (10.7)	−0.0	0.97
	Teenagers
Overall Quality of Life (CDP-QOL)1	72.7 (23.4)	70.5 (21.5)	0.5	0.63
Social subscale1	72.2 (22.8)	68.9 (19.7)	0.9	0.41
Uncertainty subscale1	75.6 (25.0)	71.4 (31.0)	0.8	0.45
Isolation subscale1	74.6 (30.2)	73.7 (24.9)	0.1	0.89
Limitations subscale1	68.5 (26.2)	69.0 (20.0)	−0.1	0.92
GF-diet Adherence (CDAT)2	12.3 (4.0)	10.7 (2.3)	1.7	0.11
Depression (CES-DC)3	10.4 (10.3)	10.5 (8.3)	−0.0	0.96
Anxiety State (STAI Children)4	48.0 (3.0)	48.1 (3.1)	−0.3	0.78
Anxiety Trait (STAI Children)4	31.4 (8.9)	33.6 (8.8)	−1.2	0.25

¹Higher scores more desirable, possible range 0 – 100; 20 items for adults, 18 items for teens; a difference of approximately 10 points higher on the CD-QOL scale or subscale implies potential clinical relevance. Dorn SD, Hernandez L, Minayas MT, et al. The development and validation of a new coeliac disease quality of life survey (CD-QOL). Aliment Pharmac Ther 2009; 31(6): 666–675; Jordan NE, Li Y, Magrini D, et al. Development and validation of a celiac disease quality of life instrument for North American children. J Pediatr Gastroenterol Nutri 2013; 57(4): 477–486.

²Lower scores more desirable, possible range 7 – 35, scores > 13 suggest inadequate adherence; 7 items; Leffler DA, Dennis M, Edwards JB, et al. A simple validated gluten-free diet adherence survey for adults with celiac disease. Clin Gastroenterol Hepatol 2009; 7(5): 530–536.

³Lower scores more desirable, possible range 0 – 60, scores > 15 suggest depression; 20 items each for adults and teens; Radloff LS. The CES-D scale: A self-report depression scale for research in the general population. Appl Psychol Meas 1977; 1(3): 385–401; Radloff LS. The use of the Center for Epidemiologic Studies Depression Scale in adolescents and young adults. J Youth Adolesc 1991; 20(2): 149–66.

⁴Lower scores more desirable, possible range 20 – 80; 40 items each for adults and teens; Spielberger CD, Gorsuch RL, Lushene R, et al. (1983). Manual for the State-Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press; Spielberger CD (1973). Manual for the State-Trait Anxiety Inventory for Children. Menlo Park, CA: Mind Garden.

⁵D.F. = 14 for Adults, D.F. = 13 for Teens (one teenager missing all follow-up data)

Over 90% of both adults and teenagers agreed that Nima was easy to understand, helped them follow a GFD, gave peace-of-mind and was useful. About 90% of adults and teenagers agreed that the capsules were hard to close. While only 47% of adults agreed that testing was time-consuming, 86% of teenagers found it to be so (χ² = 3.3, DF = 1, p = .07). More teenagers than adults agreed that using Nima made them anxious (43% versus 0.0%, χ² = 5.7, DF = 1, p = .02). The vast majority of participants would recommend the device to others with CD and planned to continue using it.

Eighty-seven percent of adults reported having the Nima indicate “gluten found” in foods they thought to be gluten-free, 77% of those reported always trusting that finding, and 69% never ate the food after such a result. Corresponding percentages for teenagers were 64%, 100%, and 89%.

Discussion

This pilot highlights benefits of and barriers to using a newly marketed gluten sensor device by individuals with CD. Nima’s convenient size/portability were appreciated. Physical difficulty with the capsules was a major drawback, especially for teenagers, who found the struggle embarrassing around friends and generally created a lack of enthusiasm. The manufacturer now offers a wrench to facilitate closing. Nearly half of participants failed to recall the device’s testing limitations; Nima cannot correctly detect gluten in fermented foods like soy sauce and barley malt. This knowledge deficit is concerning, and would likely be even greater among the general population.

Open-ended responses added nuance. In line with Nima’s intended use as “an extra layer of information” [8], participants used the device to “double” check foods believed to be gluten-free. Some reported inconsistent results upon repeat testing of the same meal. Some felt the device to be too sensitive for their personal needs. Users should be aware of Nima’s limitations, particularly for foods with gluten levels close to the 20 ppm cutoff.

This pilot had a small and demographically homogeneous sample and no control group. Having provided the device, we could not evaluate cost effects (229USD for the device; 5USD per single-use capsule, as of 2/21/19). Nevertheless, our data suggest potential beneficial effects of using the Nima on QOL and depression, at least for adults with CD.

CONSORT 2010 Flow Diagram

CONSORT 2010 checklist of information to include when reporting a pilot or feasibility trial^*

Section/Topic	Item No	Checklist item	Reported on page No
Title and abstract
	1a	Identification as a pilot or feasibility randomised trial in the title	1
	1b	Structured summary of pilot trial design, methods, results, and conclusions (for specific guidance see CONSORT abstract extension for pilot trials)	Not applicable for RC
Introduction
Background and objectives	2a	Scientific background and explanation of rationale for future definitive trial, and reasons for randomised pilot trial	5
	2b	Specific objectives or research questions for pilot trial	5
Methods
Trial design	3a	Description of pilot trial design (such as parallel, factorial) including allocation ratio	5
	3b	Important changes to methods after pilot trial commencement (such as eligibility criteria), with reasons	N/A
Participants	4a	Eligibility criteria for participants	5
	4b	Settings and locations where the data were collected	5
	4c	How participants were identified and consented	5
Interventions	5	The interventions for each group with sufficient details to allow replication, including how and when they were actually administered	5–6
Outcomes	6a	Completely defined prespecified assessments or measurements to address each pilot trial objective specified in 2b, including how and when they were assessed	6
	6b	Any changes to pilot trial assessments or measurements after the pilot trial commenced, with reasons	N/A
	6c	If applicable, prespecified criteria used to judge whether, or how, to proceed with future definitive trial	N/A
Sample size	7a	Rationale for numbers in the pilot trial	5
	7b	When applicable, explanation of any interim analyses and stopping guidelines	N/A
Randomisation:
Sequence generation	8a	Method used to generate the random allocation sequence	5
	8b	Type of randomisation(s); details of any restriction (such as blocking and block size)	5
Allocation concealment mechanism	9	Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned	5
Implementation	10	Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions	Not described due to space limitations of RC
Blinding	11a	If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how	Not described due to space limitations of RC
	11b	If relevant, description of the similarity of interventions	N/A
Statistical methods	12	Methods used to address each pilot trial objective whether qualitative or quantitative	6
Results
Participant flow (a diagram is strongly recommended)	13a	For each group, the numbers of participants who were approached and/or assessed for eligibility, randomly assigned, received intended treatment, and were assessed for each objective	Consort Flow Diagram
	13b	For each group, losses and exclusions after randomisation, together with reasons	Flow Diagram, Table 1
Recruitment	14a	Dates defining the periods of recruitment and follow-up	5
	14b	Why the pilot trial ended or was stopped	N/A
Baseline data	15	A table showing baseline demographic and clinical characteristics for each group	6 (not in table due to limits of RC)
Numbers analysed	16	For each objective, number of participants (denominator) included in each analysis. If relevant, these numbers should be by randomised group	Table 1
Outcomes and estimation	17	For each objective, results including expressions of uncertainty (such as 95% confidence interval) for any estimates. If relevant, these results should be by randomised group	Table 1
Ancillary analyses	18	Results of any other analyses performed that could be used to inform the future definitive trial	N/A
Harms	19	All important harms or unintended effects in each group (for specific guidance see CONSORT for harms)	N/A
	19a	If relevant, other important unintended consequences	N/A
Discussion
Limitations	20	Pilot trial limitations, addressing sources of potential bias and remaining uncertainty about feasibility	8
Generalisability	21	Generalisability (applicability) of pilot trial methods and findings to future definitive trial and other studies	8
Interpretation	22	Interpretation consistent with pilot trial objectives and findings, balancing potential benefits and harms, and considering other relevant evidence	7–8
	22a	Implications for progression from pilot to future definitive trial, including any proposed amendments	Not included due to space limits of RC
Other information
Registration	23	Registration number for pilot trial and name of trial registry	4
Protocol	24	Where the pilot trial protocol can be accessed, if available	4
Funding	25	Sources of funding and other support (such as supply of drugs), role of funders	1–2
	26	Ethical approval or approval by research review committee, confirmed with reference number	5

Citation: Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355.

^*We strongly recommend reading this statement in conjunction with the CONSORT 2010, extension to randomised pilot and feasibility trials, Explanation and Elaboration for important clarifications on all the items. If relevant, we also recommend reading CONSORT extensions for cluster randomised trials, non-inferiority and equivalence trials, non-pharmacological treatments, herbal interventions, and pragmatic trials. Additional extensions are forthcoming: for those and for up to date references relevant to this checklist, see www.consort-statement.org.

Abbreviations used in this manuscript:

Celiac Center

Celiac Disease Center of Columbia University

CD

celiac disease

CDAT

Celiac Dietary Adherence Test

CDSD

Celiac Disease Symptom Diary

GFD

Gluten-free Diet

QOL

quality of life

CESD

Center for Epidemiologic Studies Depressions Scale

FARRP

Food Allergy Research and Resource Program

FDA

Food and Drug Administration

ppm

parts per million

NYC

New York City

STAI

State-Trait Anxiety Inventory

USD

United States dollars