Clinical trial NCT01327300: Efficacy of Mesalamine in Diarrhea-predominant Irritable Bowel Syndrome (dIBS)
Official title: Randomized, Double-blind, Cross-over Study of the Efficacy of Mesalamine in Diarrhea-predominant Irritable Bowel Syndrome (dIBS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome
Keywords: Irritable Bowel Syndrome
Irritable Bowel Syndrome Treatment
Mesalamine
Anti-inflammatory drugs
5-ASA drugs
Apriso ™
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2011-04-01
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Changes in GIS Scores Between Baseline and After a 12 Week Intervention With Mesalamine or Placebo
timeFrame: Baseline and at 12 weeks post-intervention
Secondary outcomes:
measure: Number of Participants Who Had Evidence of Increased Levels of Pathologic Indicators of Colonic Mucosal Inflammation at 12 Weeks Compared to Baseline.
timeFrame: 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)
measure: Functional Bowel Disorder Severity Index (FBDSI)
timeFrame: 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.
measure: IBS - Quality of Life (IBS-QOL)Score.
timeFrame: 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)
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 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)
measure: Intestinal Permeability Testing
timeFrame: 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)
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Baharak Moshiree, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Drossman DA, Whitehead WE, Camilleri M. Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology. 1997 Jun;112(6):2120-37. doi: 10.1053/gast.1997.v112.agast972120. No abstract available.
citation: Sandler RS. Epidemiology of irritable bowel syndrome in the United States. Gastroenterology. 1990 Aug;99(2):409-15. doi: 10.1016/0016-5085(90)91023-y.
citation: Bjarnason I, MacPherson A, Hollander D. Intestinal permeability: an overview. Gastroenterology. 1995 May;108(5):1566-81. doi: 10.1016/0016-5085(95)90708-4.
citation: Dunlop SP, Hebden J, Campbell E, Naesdal J, Olbe L, Perkins AC, Spiller RC. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol. 2006 Jun;101(6):1288-94. doi: 10.1111/j.1572-0241.2006.00672.x.
citation: Corinaldesi R, Stanghellini V, Cremon C, Gargano L, Cogliandro RF, De Giorgio R, Bartesaghi G, Canovi B, Barbara G. Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study. Aliment Pharmacol Ther. 2009 Aug;30(3):245-52. doi: 10.1111/j.1365-2036.2009.04041.x. Epub 2009 May 12.
citation: Gordon S, Ameen V, Bagby B, Shahan B, Jhingran P, Carter E. Validation of irritable bowel syndrome Global Improvement Scale: an integrated symptom end point for assessing treatment efficacy. Dig Dis Sci. 2003 Jul;48(7):1317-23. doi: 10.1023/a:1024159226274.
citation: Zhou Q, Fillingim RB, Riley JL 3rd, Malarkey WB, Verne NG. Central and peripheral hypersensitivity in the irritable bowel syndrome. Pain. 2010 Mar;148(3):454-461. doi: 10.1016/j.pain.2009.12.005. Epub 2010 Jan 13.
citation: Myers CD, Robinson ME, Riley JL 3rd, Sheffield D. Sex, gender, and blood pressure: contributions to experimental pain report. Psychosom Med. 2001 Jul-Aug;63(4):545-50. doi: 10.1097/00006842-200107000-00004.