Clinical trial NCT01094041: Gluten Intolerance in Patients With Diarrhea Predominant Irritable Bowel Syndrome
Official title: Gluten Intolerance in Irritable Bowel Syndrome With Diarrhea: The Role of HLA-DQ2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diarrhea
Diarrhea Predominant Irritable Bowel Syndrome
Keywords: Gluten
Diarrhea or diarrhea predominant irritable bowel syndrome
Colonic permeability
Small bowel permeability
Colonic inflammatory response
Small bowel inflammatory response
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2010-03-26
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

1. Stool samples to check markers of inflammation such as fecal calprotectin.
2. Blood samples to check markers of inflammation and for genetic testing.
3. After ingestion of the mannitol, lactulose and sucralose sugars, urine samples to indirectly measure small intestinal and colonic permeability.
4. After sedation, upper gastrointestinal endoscopy and flexible sigmoidoscopy to obtain 6 mucosal biopsies from the small bowel and sigmoid colon for immunohistochemical analysis.
5. Scintigraphy to measure gastrointestinal transit.

Eligibility criteria: Inclusion criteria:

1. Diarrhea or diarrhea predominant IBS patients
2. Age 18 to 65
3. BDQ confirms presence of IBS-D or functional diarrhea, positive by Rome III criteria
4. No restrictions on Hospital Anxiety Depression score
5. No abdominal surgery (except appendectomy and cholecystectomy)

Exclusion criteria:

1. Serum tissue transglutaminase IgA or IgG positive or medical record of small bowel biopsy suggestive of celiac disease
2. Use of tobacco products within the past 6 months (since nicotine may affect intestinal permeability)
3. Use of NSAIDs or aspirin within the past week (since NSAIDs affect intestinal permeability)
4. Use of oral corticosteroids within the previous 6 weeks
5. 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
6. Ingestion of any prescription, over the counter, or herbal medications which can affect gastrointestinal transit 7 days before study begins.
7. Any females who are pregnant or trying to become pregnant (due to radiation exposure)
8. Bleeding disorders or medications that increase risk of bleeding from mucosal

Primary outcomes:
measure: Small bowel permeability
timeFrame: 0 - 2 hours post sugar ingestion
measure: Colonic permeability
timeFrame: 2 -24 hours post sugars ingestion
measure: Colonic transit
timeFrame: 24 hours
Secondary outcomes:
measure: Colon transit
timeFrame: 6-12 hours
measure: Colonic permeability
timeFrame: 2-24 hours after sugars ingestion
measure: Colonic permeability
timeFrame: 8 to 24 hours after ingestion of sugars
measure: Small bowel transit time
timeFrame: 6 hours
measure: Gastric emptying
timeFrame: 0-2 hours
measure: Colonic inflammatory response
timeFrame: 4 weeks
measure: Stool frequency and consistency
timeFrame: 6 weeks
measure: Small bowel inflammatory response
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vazquez-Roque MI, Camilleri M, Smyrk T, Murray JA, Marietta E, O'Neill J, Carlson P, Lamsam J, Janzow D, Eckert D, Burton D, Zinsmeister AR. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology. 2013 May;144(5):903-911.e3. doi: 10.1053/j.gastro.2013.01.049. Epub 2013 Jan 25.