The Efficacy of Mutaflor(E. Coli Nissle 1917, Mutaflor®) for Chronic Constipation:Multicenter Study

Study Overview
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Brief Summary
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Chronic constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. There exist effective pharmacological therapies for chronic constipation, however, many patients do not well respond to current medications. Evidence suggests that disturbance in the gastrointestinal microbiota may be implicated in chronic constipation. Although, E.coli Nissle 1917 (Mutaflor®) has been used for chronic constipation, there are limited data regarding the efficacy of E.coli Nissle 1917 (Mutaflor®) in these patients. Therefore, this study aimed to investigate the efficacy of E.coli Nissle 1917 (Mutaflor®) in patients with chronic constipation.

Conditions
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Constipation

Intervention / Treatment
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* Drug: E. coli Nissle 1917(Mutaflor®)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female outpatients aged from 20 to 75 years old. Patients meet International Congress of Gastroenterology (ROME III) clinical criteria for constipation*: A. Must include two or more of the following: Straining in > 1/4 defecations; Lumpy or hard stools > 1/4 defecations; Sensation of incomplete evacuation in 1/4 defecations; Sensation of anorectal obstruction/blockage in > 1/4 defecations; <3 defecations/week. B.Loose stools are rarely present without the use of laxatives. C.There are insufficient criteria for irritable bowel syndrome. *Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. Exclusion Criteria: Pregnant or lactating woman Known organic gastrointestinal disease Subjects who diagnosed advanced adenoma within 3 years Prior gastrointestinal surgery (except appendectomy, herniotomy) Subjects who diagnosed irritable bowel syndrome Use of one or more of listed medications within 2 weeks (Laxative, Metoclopramide, Domperidone, Itopride, Levosulpride, Cisapride, Mosapride, Tegaserod, Prucalopride, Renzapride, Erythromycin, buspirone, Sumatriptan, Alosetron, Cilansetron, ondansetron, Citalopram, Paroxetine, Baclofen, Sildenafil, Nitroglycerin) Subjects who diagnosed lactulose malabsorption Subjects who diagnosed liver cirrhosis, severe congestive heart failure, severe renal insufficiency, uncontrolled hypertension, endocrine disorder, metabolic disorder, prior malignancy, immune deficiency Suspected obstruction, gastric retention, ileus, perforation, fecal impaction or inflammatory bowel disease.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: E. coli Nissle 1917 (Mutaflor®)<br>Mutaflor® group will receive E. coli Nissle 1917 (Mutaflor®) 28mg 2T tid for initial 2 days, then E. coli Nissle 1917, Mutaflor® 4T qd for the next 26 days. | Drug: E. coli Nissle 1917(Mutaflor®)<br> <br> |
| Placebo Comparator: Matched placebo<br>Matched placebo group will receive placebo drug 28mg 2T tid for initial 2 days, then placebo 4T qd for the next 26 days. Placebo drug has same shape and size with E. coli Nissle 1917 (Mutaflor®). | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relief of constipation defined by improvement of complete spontaneous bowel movements(CSBMs/week) | Subjects will report symptoms by questionnaire | 28days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of average number of CSBMs/week | Subjects will report symptoms by questionnaire | 28days | 
| The time to 1st CSBM or SBM | Subjects will report symptoms by questionnaire | 28days | 
| Improvement of constipation related quality of life | Subjects will report symptoms by questionnaire | 28days | 
| Improvement of constipation related symptom | Subjects will report symptoms by questionnaire | 28days |