The Effect of Long-Acting Mesalamine on Post-Infective Irritable Bowel Syndrome- A Pilot Study

Principal Investigator: Ashok Tuteja
Keywords: Irritable Bowel Syndrome , Diarrhea , Mesalamine , Gastroenteritis , abdominal pain , hypersensitivity , quality of life , Post-Infectious Department: Gastroenterology
IRB Number: 00039402 Co Investigator:  
Specialty: Gastroenterology, Gastroenterology
Sub Specialties: Irritable Bowel Syndrome
Recruitment Status: Recruiting

Contact Information

Hannah  Kinnebrew
hannah.kinnebrew@hsc.utah.edu
801-581-3693

Brief Summary

Purpose: The purpose of this study is to evaluate the effects of long acting mesalamine (Lialda®) in patients with Post-Infective Irritable Bowel Syndrome (PI-IBS). We will evaluate gastrointestinal symptoms, IBS specific quality of life (IBS-QOL), and plasma cytokines before and after treatment with Lialda®.
  
This study will test long acting mesalamine in the management of PI-IBS. It has the potential to improve QOL and perhaps gastrointestinal symptoms, in patients with PI-IBS. The results of this study, if positive, will provide preliminary data for a large scale clinical trial.
 
This study will also provide information about plasma cytokines in patients with PI-IBS and whether improvement in symptoms correlates with improvement in plasma cytokines.
 

Aim: To determine if mesalamine will relieve symptoms, improve QOL and reduce inflammation in patients with PI-IBS.

Objectives:

Objective #1: Determine the efficacy of mesalamine in patients with PI-IBS.

Hypothesis: Treatment with mesalamine compared to placebo will improve QOL, and global as well as individual symptoms of IBS

 

Study End-points

Primary:

  1. Improvement in self reported overall Bowel Symptom Scores (BSS) after 8 weeks of treatment will be used as the primary endpoint.

Secondary:

  1. Change in specific bowel symptoms: bowel frequency, bowel consistency, abdominal pain, urgency, and bloating after 8 weeks treatment.
  2. IBS-QOL at end of treatment

 Definition of a Responder: Patient who report at least 50% of the weeks of treatment with satisfactory relief (30% or more reduction in symptom) will be designated as responders.

Inclusion Criteria

Ambulatory patients, 18 years of age or older with PI-IBS symptoms for at least 6 months will be enrolled in the study.  The study population will consist of previously healthy patients who developed IBS after an episode of gastroenteritis. Patients will be identified by the Bowel Disease Questionnaire which is sensitive to Rome Criteria.32 Rome III criteria will be used to define IBS. PI-IBS patients are usually diarrhea-predominant and patients whose predominant symptom is constipation will not be enrolled in this study, patients with mixed IBS will be included. Patients will be recruited from the Internal Medicine and Gastroenterology clinics at the, University Hospital and the VA Medical Center.

Inclusion Criteria

  1. Men and women age 18-75 years
  2. Rome III criteria for IBS
  3. Symptom onset after apparent acute gastroenteritis
  4. Symptoms of 6 months or greater duration
  5. Normal gross appearance of the colonic mucosa other than erythema and polyps
  6. Negative markers for celiac disease (tissue transglutaminase antibody or endomysial antibody).
  7. No clinically significant abnormality in thyroid function (Thyroid Stimulating Hormone) and serum calcium
  8. Stable medication regimens for more than 1 month.
  9. Sexually active female patient of child bearing potential have negative urine pregnancy test or  practices accepted method of birth control during the study.

 

Rome III criteria for IBS13

Recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated with two or more of the following:

  1. Improvement with defecation
  2. Onset associated with change in frequency of stool
  3. Onset associated with change in form (appearance) of stool.

Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis.

Diarrhea-predominant IBS is defined by the presence of loose (mushy) or watery stools at least 25% of times and hard or lumpy stool <25% of times (in the absence of antidiarrheal or laxative use).

Constipation-predominant IBS: hard or lumpy stools  ≥25% and loose (mushy) or watery stools <2% of bowel movements.

Mixed IBS: hard or lumpy stools ≥25% and loose (mushy) or watery stools ≥25% of bowel movements.

Unsubtyped IBS: insufficient abnormality of stool consistency to meet criteria for IBS-C, D, or M.

The validated Bristol Stool Form scale will be used to determine the participants usual stool consistency. 33

Criteria for PI-IBS

Acute onset of symptoms of IBS subsequent to two or more of the following: 1) fever, 2) vomiting, 3) diarrhea
 

Exclusion Criteria

Exclusion Criteria

  1. Age <18 or > 75 years
  2. Constipation-predominant IBS.
  3. Clinically significant chronic cardiac, pulmonary, hepatic, renal dysfunction or HIV
  4. History of/or presence of active malignancy (patients with skin and other cancers in remission for more than 5 years are allowed in study)
  5. Current evidence of any gastrointestinal disorder such as celiac disease, inflammatory bowel disease, chronic pancreatitis, scleroderma, HIV, small bowel or colonic resection, paraplegia or quadriplegia
  6. Current evidence of drug or alcohol abuse as judged by the investigator
  7. Allergy to Mesalamine or aspirin
  8. Investigator perception of patient’s inability to comply with the study protocol
  9. Unstable psychiatric disease
  10. Recent change in gastrointestinal medications