Evaluate the Efficacy, Safety and Tolerability of Fecal Microbiota Transfer for the Treatment of Patients With Nonalcoholic Steatohepatitis

Study Overview
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Brief Summary
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The EMOTION study is a multicentric, double-blind, controlled, parallel-group, phase IIa randomized Clinical trial to evaluate the efficacy, safety and tolerability of TMF capsules for the treatment of patients with NASH. The clinical trial has two stages: Screening phase with a duration of 12 weeks to classify patients based on lifestyle modifications. Treatment phase where patients will be randomized and stratified 2:1 to treatment: Experimental for n=64 patients. Placebo control for n=32 patients.

Official Title
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Randomized, Double-blind, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of Fecal Microbiota Transfer by Capsules vs. Placebo for the Treatment of Patients With Nonalcoholic Steatohepatitis

Conditions
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Patients With Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Group 1 or Experimental group
* Other: Group 2 or Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of both genders aged between 18 and75 years old (both included). Body mass index (BMI) <40 kg/m2. Histological diagnosis of NASH, accepted by EASL and AASLD , from a liver biopsy obtained up to 24 weeks prior to the signing of the informed consent. NASH histologic activity score (NAS) ≥ 4, with a score of 1 or more in each subcomponent (steatosis, lobular inflammation, and liver cell ballooning). Histologic evidence of stage 1 fibrosis (with perisinusoidal or portal fibrosis), stage 2 (perisinusoidal and portal/periportal fibrosis), or stage 3 (bridging fibrosis) as defined by the NASH CRN fibrosis score. Exclusion Criteria: Evidence of other type of liver disease. History of high alcohol intake (daily consumption > 30 g/day for men and > 20 g/day for women). Weight change of more than 5% in the 3 months prior to screening. Subjects with HbA1c> 9.5%. For subjects with an HbA1c> 9.5% at the screening visit, a repeat test may be performed within the screening window. A repeated result of HbA1c> 9.5% will result in exclusion. Diabetic patients with: Insulin treatment. Changes in antidiabetic medication in the 4 months prior to liver biopsy according to the following conditions: Modification of the dose of treatment with glucagon agonists type 1 (GLP-1). Implementation of treatment with a new antidiabetic. History of bariatric surgery. Cirrhosis. Portal thrombosis. Known or suspected hepatocellular carcinoma. Clinically significant gastrointestinal, cardiovascular, neurological, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory or infectious disease, as determined by the investigator. An estimated glomerular filtration rate (eGFR) <45 ml / min / 1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] method). Medical conditions that decrease life expectancy to less than 2 years, including cancer. Presence of an inherited or acquired immunodeficiency. Diagnosis of inflammatory bowel disease (Crohn's disease, ulcerative colitis, microscopic colitis), active irritable bowel syndrome (within the last 2 years according to Rome IV criteria), celiac disease not well controlled with a gluten-free diet, active gastroparesis, toxic megacolon. Major intra-abdominal surgery in the 2 months prior to randomization of the patient in the study. Antibiotic intake in the 8 weeks prior to the screening date. Probiotic/prebiotic/marketed synbiotic intake in the 4 weeks prior to the screening date. Pregnancy or lactation. Any other condition that, in the opinion of the investigator, could prevent or hinder compliance. Use of medication with potential steatogenic effect (corticosteroids, valproic acid, amiodarone and/or tamoxifen) within the 6 months prior to the first dose of study drug.

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 |
| --- | --- |
| Experimental: Group 1 or Experimental group<br>treatment with an initial dose of 24 oral capsules of MBK-01 and a maintenance dose of 12 oral capsules of MBK-01 every 3 months (4 maintenance doses). | Drug: Group 1 or Experimental group<br>* Capsules of fecal microbiota transplantation<br>|
| Placebo Comparator: Group 2 or Control group<br>treatment with an initial dose of 24 oral capsules of MBK-01 and a maintenance dose of 12 oral capsules of MBK-01 every 3 months for 12 months (4 maintenance doses) | Other: Group 2 or Control group<br>* capsules of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with improvement of fat fraction by proton density by MRI and no worsening of activity or fibrosis. |  | 72 weeks | 
| number of adverse events (AEs), serious AEs, AEs resulting in discontinuation of study treatment, AEs of special interest, and changes in vital signs and laboratory values |  | 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with improvement (at least one point) in lobular swelling and/or ballooning without worsening of fibrosis. |  | 72 weeks | 
| NAFLD Fibrosis score |  | 72 weeks | 
| Changes in weight, BMI. |  | 72 weeks | 
| Changes in systolic and diastolic blood pressure, lipid profile, carotid ultrasound. |  | 72 weeks | 
| Changes in the quality of life questionnaire specific to chronic liver disease due to NAFLD. |  | 72 weeks | 
| patient-reported outcomes |  | 72 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MetEH: metabolic hepatic steatosis, NASH nonalcoholic steatohepatitis, TMF: fecal microbiota transplantation