Efficacy of Mesalamine in Diarrhea-predominant Irritable Bowel Syndrome (dIBS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01327300
First received: March 24, 2011
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Irritable Bowel Syndrome
Drug: Mesalamine
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Cross-over Study of the Efficacy of Mesalamine in Diarrhea-predominant Irritable Bowel Syndrome (dIBS)

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Changes in Global Improvement Scale (GIS) scores [ Time Frame: for 23 months, At each Shands GI Clinic visit of participating patients from 03/25/2010 to 02/01/2012 ] [ Designated as safety issue: No ]
    Patients will rate the severity of their GI symptoms.


Secondary Outcome Measures:
  • Pathologic indicators of colonic mucosal inflammation [ Time Frame: 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) ] [ Designated as safety issue: No ]
    colonoscopy/felxible sigmoidoscopy will be performed and mucosal biopsies will be obtained.

  • Functional Bowel Disorder Severity Index (FBDSI) [ Time Frame: an FBDSI score is administered at the beginning of each 12-week treatment period and at the end 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) ] [ Designated as safety issue: No ]
    Subjects rate pain on a standardized scale.

  • IBS - Quality of Life (IBS-QOL) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    A questionnaire is given to each patient.

  • Symptom Checklist-90-R (SCL-90-R) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    A questionnaire is given to each patient.

  • Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    A questionnaire is given to each patient.

  • Intestinal Permeability Testing [ Time Frame: 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) ] [ Designated as safety issue: No ]
    ability of test substances to permeate the intestinal mucosa.

  • Experimental Sensory Testing [ Time Frame: 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) ] [ Designated as safety issue: No ]
    This is an additional but optional component for the study subjects who consent and includes different kinds of sensory testings.


Enrollment: 7
Study Start Date: March 2010
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: Mesalamine
Apriso is a 5-ASA drug with Intellicor ™ extended-release delivery technology. A 1.5 gram dosage of Apriso (equaling four 375 mg capsules) once a day will be administered orally for a period of 12 weeks followed by a 3 week wash out prior to crossing over to the placebo arm.
Other Name: Apriso ™
Placebo Comparator: 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.
Other: Placebo
4 capsules (.375 gm sugar pill capsules) administered orally once a day. This group will receive the placebo for 12 weeks then a wash out for 3 weeks prior to crossing over to the drug arm.
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 asparatame contained in Apriso
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01327300

Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Baharak Moshiree, MD, MS University of Florida
  More Information

Publications:

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01327300     History of Changes
Other Study ID Numbers: 106-2010
Study First Received: March 24, 2011
Last Updated: March 28, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
Irritable Bowel Syndrome
Irritable Bowel Syndrome Treatment
Mesalamine
Anti-inflammatory drugs
5-ASA drugs
Apriso ™

Additional relevant MeSH terms:
Diarrhea
Irritable Bowel Syndrome
Signs and Symptoms, Digestive
Signs and Symptoms
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Mesalamine
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 16, 2013