Role Of Lactobacillus Reuteri DSM 17938 In The Non-Complicated Diverticular Disease

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effectiveness and the tolerability of the Lactobacillus reuteri in the control of the diverticular disease symptoms and in the prevention of acute diverticulitis episodes.

Detailed Description
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The gastrointestinal apparatus hosts a bacterial population that quantifies to around 1011 microorganisms per gram of content with more than 400 different species. Its principal functions are: metabolic, trophic, and protective. The Lactobacillus reuteri (Reuterin®) is considered one of the few native species in the human intestinal tract. It is able to modulate the immune response CD4+ T-Helper to an ileum level. Lactobacillus reuteri isolated for the first time in 1980 is a heterofermantative species. Its probiotic activity is attributed to the ability to exercise an inhibitive effect on the pathogenic micro-organisms with a combination of mechanisms including the production of lactic acid, hydrogen peroxide, antimicrobic substances and bactericide. Moreover, Lactobacillus reuteri is in a position to produce various short chain-like fat acids such as the acetic acid from the fermentation of carbohydrates. At last, it is in a position to produce a powerful antimicrob substance known as Reuterina that is capable of inhibiting the growth of many bacterial species including Escherichia, Salmonella, Shigella, Proteus, Pseudomonas, Clostridium and Sfafilococcus as well as fungi and protozoa, many of which are pathogens for man. Among pathologies in which it is hypothesized that probiotics could have a possible therapeutic role, there is the diverticulosis disease. Approximately 20% of patients with colonic diverticula have intestinal disturbances and a reduction of the quality of life. Moreover approximately 20% of the patients with diverticulosis in the colon have at least 1 acute diverticulitis attack, characterized by pain, fever, abdominal defence, increment of the VES and neutrophil leucocytosis. Usually the acute diverticulitis episode can be controlled by medical therapy, but repeated episodes in time often lead to greater complications in the perforation, from the abdominal abscesses, from the fistulas and from the stenosis. The prevention of acute diverticulitis episodes is therefore very important so as to prevent greater complications of such pathology. Until now, the scientific evidences have suggested the use of fibre and non-absorbable antibiotics (such as rifaximine) for the treatment of a non-complicated diverticular disease and for the prophylaxis of the feared complications. The extended use of antibiotics exposes to the risk of selecting resistant strains and there are no long-term studies on the outcome of the patients suffering from diverticulosis in continuous therapy with rifaximine and fibres. The therapy with Lactobacillus reuteri could be effective in the control of symptoms of the diverticular disease through its trophic action on coloncytes (thanks to the SCFA production), both through the modulation of the activity of the immune system and on the intestinal permeability. Moreover the antibacterial activity of Lactobacillus reuteri against the pathogenic bacteria could be useful in the prevention and the treatment of acute diverticulitis episodes. Finally, thanks to its trophic role on the intestinal epithelium, Lactobacillus reuteri could help the mucosal cure of acute diverticulitis episodes.

Official Title
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Phase 3 Study of Lactobacillus Reuterii in Patients With Symptomatic Non-complicated Diverticular Disease

Conditions
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Diverticulosis, Diverticulitis

Intervention / Treatment
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* Dietary Supplement: Lactobacillus Reuterii
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients affected by symptomatic diverticulosis Informed consent obtained and signed. Expected compliance Exclusion Criteria: Patients supplemented with other probiotics Patients treated with antibiotics Patients affected by hearth failure, renal failure, neoplasia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lactobacillus Reuterii<br> | Dietary Supplement: Lactobacillus Reuterii<br>* Lactobacillus Reuterii 10000000000 CFU per day<br>|
| Placebo Comparator: Placebo<br> | Dietary Supplement: placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of 50% of the score of activity of the diverticular disease | A validated questionnaire was used to investigate on intestinal symptoms. The following symptoms/signs will be investigated: Abdominal pain Abdominal bloating Urgency Diarrhoea Abdominal Tension Each factor previously listed will be graded according to the following scale of gravity: 0= no symptom 1= light disturbance 2= moderate disturbance 3= serious disturbance The score of activities can range between 0 (asymptomatic patient) to 15 (serious disturbances with important impacts on the quality of life). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of 20% of acute diverticulitis episodes | To value the efficancy in reduction of acute diverticulitis, defined as episodes of abdominal pain associated with fever and/or abdominal resistance, increment of ESR and neutrophil leucocitosis and that demand a treatment of systemic antibiotics | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diverticula, Diverticular disease, Diverticulitis, Probiotics