- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01327300
Efficacy of Mesalamine in Diarrhea-predominant Irritable Bowel Syndrome (dIBS) (IBS)
Randomized, Double-blind, Cross-over Study of the Efficacy of Mesalamine in Diarrhea-predominant Irritable Bowel Syndrome (dIBS)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Florida
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Gainesville, Florida, United States, 32610
- University of Florida
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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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 Names:
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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.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
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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.
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Baseline and at 12 weeks post-intervention
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants Who Had Evidence of Increased Levels of Pathologic Indicators of Colonic Mucosal Inflammation at 12 Weeks Compared to Baseline.
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)
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Colonoscopy/flexible sigmoidoscopy will be performed and mucosal biopsies will be obtained. Each biopsy was stained for activated t lymphocytes, mast cells and eosinophils . CD117 staining was done for Mast cells. H and E staining was used to identify lymphocytes and eosinophils. Each path specimen was then noted to have increased versus normal number of these inflammatory cells. |
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)
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Functional Bowel Disorder Severity Index (FBDSI)
Time Frame: 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.
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Subjects rate pain on a standardized scale.
This is a standardized test used to evaluate patients with IBS.
Baseline values are compared to 12 weeks after mesalamine and 12 weeks after placebo treatments.
The FBDSI is score is interpreted as such: Severity of IBS is rated as none (0 points), mild (1-36 points), moderate as 37-110 points and severe as >110 points.
Therefore patients can have a score higher than 110.
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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.
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IBS - Quality of Life (IBS-QOL)Score.
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)
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A questionnaire is given to each patient and was completed at baseline then after 12 weeks of intervention with mesalamine and then placebo in the cross-over study.
The IBS-QOL comprises 34 items with 5-point response scales (0 to 4) that cover eight dimensions of HRQL: dysphoria (8 items), interference with activity (7 items), body image (4 items), health worry (3 items),food avoidance (3 items), social reaction (4 items), sexual concerns (2 items) and relationships (3 items).
Higher values indicate better HRQL after converting the raw score on the IBS-QOL into 0 to 100 points.
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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)
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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)
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A questionnaire is given to each patient with scoring done on a Likert scale ranking from 0-42 which combines anxiety and depression scales. Each of these are scored from 0-21 depending on anxiety versus the depression parameters. Comparison of change in HADs after 12 weeks of intervention with either mesalamine or placebo is provided here with only the total value provided-range is from 0-42. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 3 with zero being none at all or occasional and 3 as most of the time. The scale used is a Likert scale and therefore the data returned from the HADS is ordinal. The best score for the HADS therefore is a 0 with the worst score a 42 for combined anxiety and depression scores. For the subscales of depression and anxiety, the best score is a 0 and the worst is a 21. This data is not provided here. Data below includes the change from baseline in the HADS scores. |
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)
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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)
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Ability of test substances to permeate the intestinal mucosa. The Lactulose/Mannitol test (Genova Diagnostics®, Ashville, NC) directly measures the ability of mannitol and lactulose to permeate the intestinal mucosa. Patient ingests 5 grams of lactulose and 2 grams of mannitol dissolved in a 100 ml of water. Urine is then collected for 24 hours and the ratio of the urinary excretion of lactulose to mannitol is measured. This testing is performed only after completion of each treatment period , after 12 weeks of mesalamine and after 12 weeks of placebo. Normal ratio of lactulose/mannitol is any value <0.7. An abnormal ratio is defined as >0.7 ratio. The lactulose is measured in the urine as g/kg and the urinary excretion of mannitol is also measures as g/kg. |
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)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Baharak Moshiree, MD, MS, University of Florida
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. Erratum In: Am J Gastroenterol. 2006 Aug;101(8):1944.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Disease
- Signs and Symptoms, Digestive
- Gastrointestinal Diseases
- Colonic Diseases, Functional
- Colonic Diseases
- Intestinal Diseases
- Syndrome
- Irritable Bowel Syndrome
- Diarrhea
- Physiological Effects of Drugs
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Mesalamine
Other Study ID Numbers
- 106-2010
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Vasily IsakovRussian Science Foundation; Azbuka vkusa; Federal Research Centre of Nutrition...CompletedIrritable Bowel Syndrome With Constipation | Constipation-predominant Irritable Bowel SyndromeRussian Federation
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