Efficacy of Mesalamine in Diarrhea-predominant Irritable Bowel Syndrome (dIBS)
Palabras clave
Abstracto
Descripción
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.
fechas
| Verificado por última vez: | 12/31/2013 |
| Primero enviado: | 03/23/2011 |
| Inscripción estimada enviada: | 03/30/2011 |
| Publicado por primera vez: | 03/31/2011 |
| Última actualización enviada: | 01/14/2014 |
| Última actualización publicada: | 02/11/2014 |
| Fecha de los primeros resultados enviados: | 04/03/2013 |
| Fecha de los primeros resultados de CC enviados: | 01/14/2014 |
| Fecha de los primeros resultados publicados: | 02/11/2014 |
| Fecha de inicio real del estudio: | 02/28/2010 |
| Fecha estimada de finalización primaria: | 02/29/2012 |
| Fecha estimada de finalización del estudio: | 02/29/2012 |
Condición o enfermedad
Intervención / tratamiento
Drug: Mesalamine
Other: Placebo
Fase
Grupos de brazos
| Brazo | Intervención / tratamiento |
|---|---|
| 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. |
| 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. |
Criterio de elegibilidad
| Edades elegibles para estudiar | 18 Years A 18 Years |
| Sexos elegibles para estudiar | All |
| Acepta voluntarios saludables | si |
| Criterios | 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 |
Salir
Medidas de resultado primarias
1. Changes in GIS Scores Between Baseline and After a 12 Week Intervention With Mesalamine or Placebo [Baseline and at 12 weeks post-intervention]
Medidas de resultado secundarias
1. 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)]
2. 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.]
3. 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)]
4. 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)]
5. 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)]
