Lactobacillus Reuteri DSM 17938 in Functional Constipation

Study Overview
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Brief Summary
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The diffusion of gastrointestinal (GI) chronic diseases is significantly increased during the last century in western countries. In the USA and Northern Europe, constipation is twofold the prevalence found in the East and Southern Europe. In Italy, constipation affects up to 15-17% of the whole adult population. Of them, more than half (about 10%) treats this disorder by assuming laxatives, while the remaining does not even assume drugs. A close relationship between intestinal environment and bacterial flora has been found. As a matter of fact changes in the intestinal physiology can modify the composition of bacterial flora as well as modifications in the intestinal microbiota can modify the physiology of the gut. The probiotic effects on the GI motility can be due to substances released by bacteria and/or products of their fermentation. Also, probiotic may indirectly act by the release of neuroendocrine factors and/or substances released by the immune system. Clinically, it has already been demonstrated that probiotics exert a positive effect on symptoms and intestinal habit in constipated IBS patients. In this framework, the idea to perform a long lasting intervention study in patients with functional constipation treated with probiotics sounds convincing. The present study is a randomized, double blind, placebo controlled, monocentric study, concerning the evaluation of efficacy of 3 months administration of Lactobacillus reuteri DSM 17938 in patients with functional constipation, as defined by the Rome criteria. Clinical, physiological, hematological and immunologic variables will be evaluated.

Official Title
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Effect of Lactobacillus Reuteri DSM 17938 on Gut Motility in Patients With Functional Constipation

Conditions
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Functional Constipation

Intervention / Treatment
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* Dietary Supplement: L. reuteri DSM 17938
* Other: Placebo Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfilment of the Rome Criteria III for functional constipation Availability of at least one GI imaging study during the last five years (colonoscopy, sigmoidoscopy, abdominal ultrasound, barium enema) Commitment to availability for the whole study period Exclusion Criteria: Major abdominal surgery Presence of any concomitant diseases such as organic GI diseases and/or lactose and gluten intolerance; medical or psychiatric illness Alarming symptoms (rectal bleeding, weight loss, etc) Family history of peptic ulcer, colorectal cancer, or IBD Abnormal laboratory data or thyroid function.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L. reuteri DSM 17938<br> | Dietary Supplement: L. reuteri DSM 17938<br>* L. reuteri will be administered at 1x10^8 CFU dosage in form of tabs. In order to ensure colonization (run in), 4 tabs will be administered per os daily (4x10^8CFU/die) for 15 days. Then administration will continue with 2 tabs daily (2x10^8 CFU/die) for 90 days.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo Group<br>* Placebo tabs identical in form, taste and consistency to active tabs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in gastrointestinal symptoms after 3 months of probiotic administration | Validated and structured questionnaires to evaluate gastrointestinal symptoms, to confirm functional constipation diagnosis and to exclude IBS variant constipation. Score of gastrointestinal symptoms with Gastrointestinal Symptom Rating Score (GSRS); Constipation Symptom Score (CSS); Constipation QoL, Constipation Rome criteria, Diary for the symptoms and for intestinal behavior. These questionnaires will be administered at baseline, after 45 days of treatment, and at the end of treatment. | Before the start of the study (Time 0) and after 90 days of treatment (Time 90) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in metabolic parameters after 3 months of probiotic administration | Lipidic and glucidic profile; evaluation of circulating immunological parameters, short chain fatty acid (SCFA)faecal concentrations. The evaluations will be performed at baseline, after 45 days of treatment and at the end of treatment. | Before the start of the study (time 0) and after 90 days of treatment (Time 90) | 
| Changes in physiological parameters after 3 months of probiotic administration | Physiological parameters: Quali/Quantitative evaluation of the colonic transit time (TTC) with radiopaque markers (qualitative study : RX after 3 days from the 20 markers assumption. Quantitative study: RX after 3 days from the assumption of 10 markers a day for 6 days in patients with TTC delayed), non invasive evaluation of gastric electrical activity and gastric emptying time (cutaneous electrography (EGG) and 13C octanoic acid breath test). The evaluations will be performed at baseline, after 45 days of treatment and at the end of treatment | Before the start of the study (Time 0) and after 90 days of treatment (Time 90) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Functional Constipation, Functional Foods, Probiotics, Lactobacillus reuteri