Interest in Combo (a Combination of Dietary Supplements Including Probiotics) in NASH Improvement

Study Overview
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Brief Summary
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The aim of this bicentre, prospective, placebo-controlled, double-blind, randomized, interventional study is to assess for the first time the effects of a Combo with probiotics and dietary supplements compared to placebo for non-alcoholic steatohepatitis (NASH) patients with mild or severe fibrosis.

Detailed Description
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Liver-related mortality is increased 10-fold in NASH patients compared with the general population. Currently, there are no established pharmacotherapies for NASH patients. The gut microbiota has a major contributing role in the development of NASH with leaky gut, inflammation, oxidative stress and impaired microbiota. Restoring the microbiota symbiosys could be a new way of resolution of NASH. The aim of this trial is to evaluate the efficacy of the Combo, association of probiotics (Lactobacillus rhamnosus GG, Bifidobacterium breve BR03, Lactobacillus plantarum) and Glutamine, Quercetin, Vitamin E, Curcumin, Silybin, Pectin by means of histological resolution of NASH without progression of fibrosis, after 26 weeks (6 months), in 60 NASH patients with mild to severe fibrosis. To confirm a histological diagnosis of NASH and proof efficacy of the Combo, a liver biopsy will be performed prior to screening as well as at the end of supplemental phase

Official Title
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Interest in Combo (a Combination of Dietary Supplements Including Probiotics) in NASH Improvement

Conditions
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NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Dietary Supplement: Treatment with Combo
* Other: Treatment with placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of moderate to severe NASH : chronic liver disease: biological abnormalities for more than 6 months characteristic ultrasound aspects metabolic syndrome liver stiffness assessed by FibroScan between 8 and 15kPa Adults Affiliated to a social security Women using effective contraception (hormonal or mechanical) for the duration of the srudy Exclusion Criteria: Pregnancy Excessive alcohol consumption (>100g/week) Cirrhosis (elastometry > 15kPa) hepato-cellular carcinoma Hepatitis from Corticosteroids, Methotrexate, Amiodarone, Tamoxifen Viral hepatitis Auto immune hepatitis anticoagulant therapy antibiotics in the month prior to inclusion allergic to soya, aspirin, fish, E110 dye, Maltodextrin poorly controlled diabetes (Glycated Hemoglobin >8%) inclusion in a drug interventional trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment with Combo<br>3 dietary supplements will be given | Dietary Supplement: Treatment with Combo<br>* Treatment with Combo<br>|
| Placebo Comparator: Treatment with Placebo<br>3 placebos will be given | Other: Treatment with placebo<br>* Treatment with placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NASH reduction: the main expected benefit is resolution of NASH, and no worsening of fibrosis | Evolution of the SAF score and CAP elastometry, a composite histological score taking into account the improvement of Steatosis, histological activity and liver fibrosis | At 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial correlation of NASH parameters (FIB4, NAFLD and liver stiffness) and symbiosis parameters (stool analysis by Shallow Shotgun, biological data specific to symbiosis). |  | At the screening | 
| Follow up of transaminase levels |  | At 6 months | 
| Reduction of hepatic steatosis measured by CAP elastometry and Hepatic MRI |  | At 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Combo, liver stiffness, gut microbiota, dietary supplements