Clinical trial NCT06249763: Effects of Gluten Free Diet in Ulcerative Colitis
Official title: Effects of Dietary Gluten on Gastrointestinal Symptoms in Ulcerative Colitis: a Randomised Crossover Trial.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Inflammatory Bowel Diseases
Ulcerative Colitis
Keywords: Biomarkers
Treatment outcome
Gluten
Diet
Microbiome
Gastrointestinal symptoms
Fatigue
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
name: Colitis-Crohn Foreningen
name: Hospital of Southern Jutland
name: University Hospital Bispebjerg and Frederiksberg
First posted: 2024-02-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: The goal is to evaluate gastrointestinal symptoms and fatigue levels during a period of eating gluten free compared to a period of high gluten consumption in individuals with confirmed Ulcerative Colitis, and to identify clinical characteristics in the blood and microbiome of those improving from a gluten free diet. The main questions, the project aims to answer are:

* What is the effect of eating gluten free on patient-reported gastrointestinal symptoms in patients with Ulcerative Colitis?
* What is the effect of eating gluten free on patient-reported fatigue levels in patients with Ulcerative Colitis?
* What are clinical differences between those improving and not improving on fatigue levels and gastrointestinal symptoms?

During two study periods of one week each, participants will be eating gluten free supplemented with daily granola bars without and with high gluten content, respectively. During each active week, participants are asked to:

* Eat gluten free and two daily granola bars delivered by the research team
* Collect blood, stool and urine samples
* Answer questionnaires about their symptoms, disease course, habitual lifestyle, and compliance to the protocol

Detailed description: Introduction: To meet the growing demand for lifestyle recommendations among patients Ulcerative Colitis (UC) for managing their symptoms and wellbeing, this study aims to evaluate the use of the gluten free diet in the management of UC. Exposure to gluten can activate pro-inflammatory signals in the epithelium that induce mucosal damage, and the protein has previously been associated with disease activity in inflammatory bowel disease, including UC. A suggested pathway for the interaction between disease course and gluten intake is via mucosal damage followed by a flow of pathogens across the intestinal barrier.

To our knowledge, the effect of gluten on UC disease course is not fully understood, and clinical characteristics of patients benefitting from the gluten free diet has not yet been studied. To the patients, fatigue and pain from the gastrointestinal tract are the most burdensome symptoms of UC affecting life quality and restricting everyday activities for the patients. Hence, this study aims to evaluate the effects of dietary gluten in the management of gastrointestinal symptoms and fatigue in UC, and to identify clinical characteristics of patients with UC benefitting from eating gluten free.

Design: In this crossover randomized trial, the outcomes will be assessed after a one-week period of a high-gluten diet and a one-week period of a gluten free diet. Participants and study personnel will be blinded to the dietary intake by granola bars supplementing a complete gluten free diet. The intake of dietary fibres and fructans will be controlled and monitored and controlled for.

Setting: Participants will be recruited from the outpatient clinics for Gastrointestinal Diseases at Hospital Sønderjylland (Hospital of Southern Jutland) in the city of Aabenraa from from January to May 2024. Data collection will be completed in 2024.

Clinical data consist of personal data, patient-reported data on disease activity, gastrointestinal symptoms, fatigue level, health related quality of life and dietary intake, biomarkers in blood, urine and faeces, and protocol compliance measures. Information registered by clinicians and technicians will be transferred from paper format to electronic format using either double entry of data or automated forms processing.

Biologic material consist of blood, faeces and urine samples. All data are treated confidentially and stored according to the Danish Data Protection Regulation and Data Protection Law.

Sample size considerations: Sample size estimation was based on a 1.00 difference in the gastrointestinal symptoms score with a standard deviation (SD) of 1.80 which at a 5% significance level (two-sided) and with 80% statistical power would require a sample size of 28 completing participants. Consequently it was decided to aim for a total sample size of 30 participants, corresponding to a statistical power of 84%.

Project organization: The project is part of a PhD (doctor of philosophy) study. Collaborators are specialists from the gastrointestinal, biochemical and microbiology departments involved in the project and professors in biostatistics and food sciences.

The study is approved by the local Ethics Committee (S-20210174) and the local Data Agency (22/39335). The study findings will be disseminated in peer-reviewed journals, via patient associations, and presented at national and international conferences.

Eligibility criteria: Inclusion Criteria:

* Diagnosis: Ulcerative Colitis (UC)
* Language: Can read and understand Danish
* Treatment: No intention to change dose of, begin, or switch medication and biologic treatment within one month after inclusion
* Treatment: Medical and/or biologic treatment type and dose stable for at least 8-16 weeks prior to inclusion depending on the type of treatment

Exclusion Criteria:

* Age: \<18 years
* Severe disease activity defined by 6 or more bloody stools per day and/or night and one of the following: fever, pulse ≥ 90, C-reactive protein (CRP) ≥ 30mg/L by the time of inclusion
* Treatment: Have received antibiotic treatment within 4 weeks prior to inclusion
* Treatment: Previous operation for UC
* Concomitant diagnoses: Coeliac Disease (positive Immunoglobolin A against transglutaminase, TGA-IgA) or any cancer diagnosis
* Other: Taking probiotics, are pregnant or breastfeeding, or have nut or wheat allergy

Primary outcomes:
measure: Gastrointestinal symptoms
timeFrame: 1 week
Secondary outcomes:
measure: Fatigue
timeFrame: 1 week
measure: Disease activity
timeFrame: 1 week
measure: Symptom burden
timeFrame: 1 week
measure: Functional status
timeFrame: 1 week
measure: Disease-related health burden
timeFrame: 1 week
measure: General well-being
timeFrame: 1 week
measure: Joint pain
timeFrame: 1 week
measure: Stool consistency
timeFrame: 1 week
measure: Faecal Calprotectin (f-Cal)
timeFrame: 1 week
measure: C-reactive protein (CRP)
timeFrame: 1 week
measure: Serum-Zonulin
timeFrame: 1 week
measure: Faecal-Zonulin
timeFrame: 1 week
measure: Dietary compliance: diet intake
timeFrame: 1 week
measure: Urine-Gluten Immunogenic Peptides (GIP)
timeFrame: 1 week
Other outcomes:
measure: Microbiome data
timeFrame: 1 week
measure: Potential biomarkers
timeFrame: 1 week
Locations:
city: Aabenraa
country: Denmark
facility: Hospital of Southern Jutland
Study officials:
affiliation: University of Southern Denmark
name: Vibeke Andersen, Prof
role: PRINCIPAL_INVESTIGATOR
References: