Randomized, Double-blind, Cross-over Study of the Efficacy of Mesalamine in Diarrhea-predominant Irritable Bowel Syndrome (dIBS)
Overview
- Phase
- Phase 2
- Intervention
- Mesalamine
- Conditions
- Irritable Bowel Syndrome
- Sponsor
- University of Florida
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- Changes in GIS Scores Between Baseline and After a 12 Week Intervention With Mesalamine or Placebo
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
The purpose of this study is to find whether treating patients with diarrhea predominant Irritable Bowel Syndrome (IBS) with an anti-inflammatory drug called Mesalamine will help improve their symptoms of diarrhea, bloating and abdominal pain.
Detailed Description
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder affecting about 20% of the United States population and comprising almost 50% of referrals to gastroenterology practices. Although the pathophysiology of IBS is poorly understood, more recently, both inflammation and an increased intestinal permeability have been identified as potential factors in the etiology of diarrhea-predominant IBS patients(dIBS). Despite the potential of an inflammatory etiology for IBS, few studies have examined the efficacy of anti-inflammatory agents such as mesalamine in patients with IBS. The primary objective of our study is to determine the efficacy of Apriso™ (Salix Pharmaceuticals Inc), a long-acting mesalamine, in the treatment of patients with dIBS. Apriso™, is a mesalamine approved by the Food and Drug Administration (FDA) on October 31, 2008 for the maintenance of remission in patients with active, mild to moderate ulcerative colitis. The investigators will perform a randomized, double-blind, cross-over trial of mesalamine compared to placebo in patients with dIBS. This study will analyze both the objective and subjective measures of improvement in IBS symptoms. The subjective measures will include improvements in the overall symptom severity scores and the Global Improvement Scale (GIS) and the objective measures will include histological measures of inflammation as well as improvements in the intestinal membrane permeability of treated subjects. The investigators will demonstrate that during the 12 weeks treatment period with mesalamine, subjects will have improvements in their overall symptom scores, GIS scores, and will have a reduction in intestinal inflammation and also prohibit a likely improvement in Intestinal membrane permeability.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female aged 18-65 years old
- •Functional Bowel Disorder Severity Index Score above 37
- •Normal complete blood count, liver function studies and renal function studies
- •Serologies done to rule out Celiac Spure or patient has prior negative EGD with small bowel biopsies which have been negative
- •Infectious diarrhea ruled out by stool studies
- •Negative colonoscopy
Exclusion Criteria
- •Any history of chronic liver disease, heart disease, pulmonary or renal disease
- •Abnormal EKG
- •Women with positive pregnancy tests
- •Patient on steroids, antacids, or warfarin or chronic pain conditions other than fibromyalgia
- •Patients who drink over 2oz alcohol/day on a regular basis Any other causes for diarrhea such as IBD, microscopic colitis, celiac disease, history of abdominal obstruction, pancreatitis, ileus, or any gastrointestinal bleeding.
- •Patients with active malignancy in the past five years
- •Patient with any history of hypersensitivity reactions to salicylate containing medications due to cross-sensitivity with mesalamine or allergy to mesalamine medications in the past
- •Any subjects with fibromyalgia will be excluded from the pain testing portion only
- •History of Phenylketonuria due to the aspartame contained in Apriso
Arms & Interventions
Mesalamine
This group received the drug Mesalamine for 12 weeks then a wash out for 3 weeks prior to crossing over to the placebo arm.
Intervention: Mesalamine
Placebo
This group will receive the Placebo for 12 weeks then a wash out for 3 weeks prior to crossing over to the drug arm.
Intervention: Placebo
Outcomes
Primary Outcomes
Changes in GIS Scores Between Baseline and After a 12 Week Intervention With Mesalamine or Placebo
Time Frame: Baseline and at 12 weeks post-intervention
Patients rated the severity of their GI symptoms. The GIS scale goes from 1 to 7 with 1 being the worse and 7 as the best score showing improvement in symptoms. The GIS was performed at week one and at week 12 during each of the interventions. The comparisons below list the mean difference for each intervention from baseline (BL) with standard deviations then we list the p-value for the differences of baseline to intervention are reported using the Mann-Whitney test with a two-tailed p value provided.
Secondary Outcomes
- Number of Participants Who Had Evidence of Increased Levels of Pathologic Indicators of Colonic Mucosal Inflammation at 12 Weeks Compared to Baseline.(For 2 times: First time: at the time of patient recruitment in the study Second time: after the completion of first 12-week treatment period, all of which are during the time period from 02/25/2010 to 02/01/2012 (up to 2 years))
- IBS - Quality of Life (IBS-QOL)Score.(at the time of recruitment and after completion of each 12-week treatment period, all of which are during the time period from 03/25/2010 to 02/01/2012 (up to 2 years))
- Functional Bowel Disorder Severity Index (FBDSI)(An FBDSI score is administered at the beginning of each 12-week treatment period (baseline) and at the end of each 12-week treatment period.)
- Hospital Anxiety and Depression Scale (HADS)(at the time of recruitment and after completion of each 12-week treatment period, all of which are during the time period from 03/25/2010 to 02/01/2012 (up to 2 years))
- Intestinal Permeability Testing(At the completion of each 12-week treatment period, all of which are during the time period from 03/25/2010 to 02/01/2012 (up to 2 years))