Clinical trial NCT03869359: The Effect of Gluten in Patients With Irritable Bowel Syndrome and Healthy Volunteers
Official title: The Effect of Gluten in Patients With Irritable Bowel Syndrome and Healthy Volunteers: a Randomized, Placebo-controlled Double-blind Cross-over Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Keywords: gluten-free diet
gluten-containing diet
microbiota
metabolomics
healthy volunteers
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
First posted: 2019-03-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, Double-blind, Placebo-controlled, Cross-over Trial
Primary purpose: SUPPORTIVE_CARE

Brief summary: Patients with Irritable Bowel Syndrome (IBS) often link their symptoms to foods. Interest in dietary management recently increased, including the use of a gluten-free diet.

To investigate relation of gluten-free diet (GFD) and IBS, a randomized, double-blind, placebo-controlled cross-over trial will be carried out in adults (\>18) and patients with IBS according to Rome IV criteria. The aim is to assess gluten-free versus gluten-containing diet in IBS patients and Healthy Volunteers.

Detailed description: The study is a randomized, double-blind, placebo-controlled, cross-over trial.

The aim is to assess the effects of gluten-free diet (GFD) compared to gluten-containing diet (GCD) in IBS patients and Healthy Volunteers on gastrointestinal symptoms, visceral sensitivity, bacterial fermentation, psychological factors and quality of life. The primary hypothesis is that GFD decreases gastrointestinal symptoms compared to GCD and that this change is accompanied with reduced visceral sensitivity and change in bacterial fermentation. The secondary hypothesis is that GFD positively influences psychological factors and quality of life.

IBS patients (Rome IV) and Healthy Volunteers are challenged with gluten in this randomized, double-blind, placebo-controlled, cross-over study. They start with GFD or GCD and cross over to the other intervention (both for 14 days). In between there is a wash-out period of at least 14 days. The subjects will get gluten-free meals (lunch and dinner) and have to sprinkle powder over the meals, concealed in sachets with either gluten (vital gluten) or placebo (rice starch). The subjects will follow a strict GFD during the GFD and GCD periods. The subjects will eat and drink as before the study during the washout period.

Primary outcomes are change in gastrointestinal symptoms, assessed by questionnaires, including IBS Severity Scoring System (IBS-SSS) and Gastrointestinal Symtom Rating Scale-IBS (GSRS-IBS). A 50-point reduction in IBS-SSS indicates clinical response. Bacterial fermentation (exhaled hydrogen and methane) and visceral sensitivity will be measured using the Lactulose-Nutrient Challenge Test. Secondary outcomes are change in psychological factors and quality of life assessed by questionnaires, including CSI, HADS, HSPS, IBSQOL, PHQ-15 and VSI.

Eligibility criteria: Inclusion Criteria:

* Adult patients with IBS according to Rome IV criteria

Exclusion Criteria:

* allergy or documented intolerance to food,
* severe cardiovascular, hepatic, neurological or psychiatric disease
* serious gastrointestinal disease: including celiac disease and inflammatory bowel diseases (IBD),
* diabetes
* bowel dysfunction related to previous surgery
* pregnant or lactating women
* usage of antibiotics within 4 weeks before inclusion
* strict avoidance of foods

Primary outcomes:
measure: Change in Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS)
timeFrame: Baseline(day 0), day 14, day 28, day 42
measure: Change in Gastrointestinal Symptom Rating Scale - Irritable Bowel Syndrome (GSRS-IBS)
timeFrame: Baseline(day 0), day 14, day 28, day 42
measure: Change in stool frequency, measured by Bristol Stool Form (BSF)
timeFrame: Day 14, Day 42
measure: Change in Visceral Sensitivity and Bacterial Fermentation
timeFrame: Baseline(day 0), day 14, day 28, day 42
Secondary outcomes:
measure: Change in Central Sensitization Inventory (CSI) score
timeFrame: Baseline(day 0), day 14, day 28, day 42
measure: Change in Hospital Anxiety and Depression Scale (HADS) score
timeFrame: Baseline(day 0), day 14, day 28, day 42
measure: Change in Highly Sensitive Person Scale (HSPS)
timeFrame: Baseline(day 0), day 14, day 28, day 42
measure: Change in Irritable Bowel Syndrome Quality of Life Questionnaire (IBSQOL)
timeFrame: Baseline(day 0), day 14, day 28, day 42
measure: Change in Patient health questionnaire-15 (PHQ-15)
timeFrame: Baseline(day 0), day 14, day 28, day 42
measure: Change in Visceral Sensitivity Index (VSI)
timeFrame: Baseline(day 0), day 14, day 28, day 42
measure: Change in immunological profile of frozen serum samples
timeFrame: Baseline(day 0), day 14, day 28, day 42
measure: Change in metabolic profile of frozen urine samples
timeFrame: Baseline(day 0), day 14, day 28, day 42
measure: Change in microbiota content of frozen fecal samples
timeFrame: Baseline(day 0), day 14, day 28, day 42
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Magnus Simrén
state: Västra Götland
Study officials:
affiliation: Sahlgrenska University Hospital
name: Magnus Simrén, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Algera JP, Magnusson MK, Ohman L, Storsrud S, Simren M, Tornblom H. Randomised controlled trial: effects of gluten-free diet on symptoms and the gut microenvironment in irritable bowel syndrome. Aliment Pharmacol Ther. 2022 Nov;56(9):1318-1327. doi: 10.1111/apt.17239. Epub 2022 Sep 29.