Gluten Intolerance in Patients With Diarrhea Predominant Irritable Bowel Syndrome

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

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.

Study Overview

• Status: Completed
• Conditions: Diarrhea; Diarrhea Predominant Irritable Bowel Syndrome
• Intervention / Treatment: Other: Gluten free diet; Other: Gluten rich diet

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gluten free diet	Other: Gluten free diet; A 4-week gluten free diet provided
Experimental: Gluten rich diet	Other: Gluten rich diet; A 4-week gluten rich diet is provided

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

Collaborators and Investigators

• Sponsor: Mayo Clinic

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: March 25, 2010
• First Submitted That Met QC Criteria: March 25, 2010
• First Posted (Estimate): March 26, 2010

Study Record Updates

• Last Update Posted (Estimate): May 10, 2013
• Last Update Submitted That Met QC Criteria: May 8, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Gluten; Diarrhea or diarrhea predominant irritable bowel syndrome; Colonic permeability; Small bowel permeability; Colonic inflammatory response; Small bowel inflammatory response
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Malabsorption Syndromes; Syndrome; Irritable Bowel Syndrome; Diarrhea; Celiac Disease
• Other Study ID Numbers: 09-007344