Gluten Intolerance in Patients With Diarrhea Predominant Irritable Bowel Syndrome

Study Overview
=================
Brief Summary
-----------------
The specific hypotheses are: Gluten supplementation for four weeks increases small intestinal permeability and accelerates colonic transit in patients with irritable bowel syndrome with diarrhea (IBS-D) or functional diarrhea (FD) who are HLA-DQ2 positive.

Detailed Description
-----------------
The study design is a double-blind, randomized, controlled, parallel-group, 6-week study comparing the effects of gluten rich versus gluten free diets in diarrhea or diarrhea predominant IBS patients. All participants will keep a daily bowel pattern diary throughout the study. All participants will have negative serum tissue transglutaminase (TTg) assay, and anti-endomysial antibody test, if TTg is positive or equivocal. All participants will have the following studies performed both before and after the 4-week dietary intervention: Stool samples to check markers of inflammation such as fecal calprotectin. Blood samples to check markers of inflammation and for genetic testing. After ingestion of the mannitol, lactulose and sucralose sugars, urine samples to indirectly measure small intestinal and colonic permeability. After sedation, upper gastrointestinal endoscopy and flexible sigmoidoscopy to obtain 6 mucosal biopsies from the small bowel and sigmoid colon for immunohistochemical analysis. Scintigraphy to measure gastrointestinal transit.

Official Title
-----------------
Gluten Intolerance in Irritable Bowel Syndrome With Diarrhea: The Role of HLA-DQ2

Conditions
-----------------
Diarrhea, Diarrhea Predominant Irritable Bowel Syndrome

Intervention / Treatment
-----------------
* Other: Gluten free diet
* Other: Gluten rich diet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Diarrhea or diarrhea predominant IBS patients Age 18 to 65 BDQ confirms presence of IBS-D or functional diarrhea, positive by Rome III criteria No restrictions on Hospital Anxiety Depression score No abdominal surgery (except appendectomy and cholecystectomy) Exclusion criteria: Serum tissue transglutaminase IgA or IgG positive or medical record of small bowel biopsy suggestive of celiac disease Use of tobacco products within the past 6 months (since nicotine may affect intestinal permeability) Use of NSAIDs or aspirin within the past week (since NSAIDs affect intestinal permeability) Use of oral corticosteroids within the previous 6 weeks Ingestion of artificial sweeteners such as SplendaTM (sucralose), Nutrasweet TM(aspartame), lactulose or mannitol 2 days before the study begins, e.g., foods to be avoided are sugarless gums or mints and diet soda Ingestion of any prescription, over the counter, or herbal medications which can affect gastrointestinal transit 7 days before study begins. Any females who are pregnant or trying to become pregnant (due to radiation exposure) Bleeding disorders or medications that increase risk of bleeding from mucosal

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gluten free diet<br> | Other: Gluten free diet<br>* A 4-week gluten free diet provided<br>|
| Experimental: Gluten rich diet<br> | Other: Gluten rich diet<br>* A 4-week gluten rich diet is provided<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Small bowel permeability | Excretion of mannitol 0-2 hours after liquid formulation | 0 - 2 hours post sugar ingestion | 
| Colonic permeability | Cumulative excretion of mannitol at 2-24 hours after liquid | 2 -24 hours post sugars ingestion | 
| Colonic transit | Colonic transit geometric center at 24 hours | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Colon transit | Ascending colon emptying T1/2 | 6-12 hours | 
| Colonic permeability | Cumulative excretion of lactulose | 2-24 hours after sugars ingestion | 
| Colonic permeability | Hourly excretion of mannitol | 8 to 24 hours after ingestion of sugars | 
| Small bowel transit time | Colonic filling at 6 hours (%) | 6 hours | 
| Gastric emptying | Gastric emptying T1/2 | 0-2 hours | 
| Colonic inflammatory response | Sigmoid colon mucosal immunocyte count in lamina propria | 4 weeks | 
| Stool frequency and consistency | Bowel pattern diary | 6 weeks | 
| Small bowel inflammatory response | Duodenal mucosal immunocyte count in lamina propria | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gluten, Diarrhea or diarrhea predominant irritable bowel syndrome, Colonic permeability, Small bowel permeability, Colonic inflammatory response, Small bowel inflammatory response