Clinical Trial to Evaluate the Efficacy of Metadoxine as a Therapy for Patients With Non-alcoholic Steatohepatitis

Study Overview
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Brief Summary
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The aim of this study is to evaluate the efficacy of metadoxine as a therapy for patients with biopsy-proven non-alcoholic steatohepatitis.

Detailed Description
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Type and design of the study: A randomized, placebo-controlled, double-blind, clinical trial to evaluate the efficacy of metadoxine as a therapy in patients with biopsy-proven nonalcoholic steatohepatitis. Population: Non-diabetic patients with nonalcoholic steatohepatitis diagnosed by liver biopsy through the nonalcoholic fatty liver disease activity score (NAS)> 3. Sample size: Considering a difference of at least 30% between groups, a confidence level of 95% (two-sided, significance 0.05), a statistical power of 80%, and an additional 20% for possible losses, we need 54 patients per group. Variables: Independent: Treatment group (metadoxine / placebo). Dependents: Nonalcoholic fatty liver disease activity score (NAS):0 a 8 Degree of liver steatosis: 0 a 3 Degree of lobular inflammation: 0 a 3 Degree of ballooning: 0 a 2 Degree of fibrosis: 0 a 2 Weight: Kg Body mass index: Kg/m2 Waist circumference: cm Serum alanine aminotransferase: U/L Serum aspartate aminotransferase: U/L Methods: Those meeting the selection criteria will be invited to participate in this study, those who agree to participate must sign the consent form and will be randomized to placebo or metadoxine group. The duration of the therapy will be 6 months and after this period a second liver biopsy will be performed to assessed the improvement on liver histology.

Official Title
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Clinical Trial to Evaluate the Efficacy of Metadoxine as a Therapy for Patients With Non-alcoholic Steatohepatitis

Conditions
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Non-alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: metadoxine
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-diabetic patients, Overweight or with obesity degrees I, II or III according to WHO criteria (BMI ≥ 25), With evidence of liver steatosis in the ultrasonography, With biopsy-proven nonalcoholic steatohepatitis, with ≥ 3 in the NAS score (at least 1 point for liver steatosis, at least 1 point for lobular inflammation, and at least 1 point for ballooning), With or without fibrosis in the liver biopsy, but if it is present must be ≤ 2 on a scale of 4, where 4 is equivalent to cirrhosis. Exclusion Criteria: Cirrhosis, Diabetes, Heavy alcohol intake ( ≥ 20 g / day), ≥ 8 points in the Alcohol Use Disorders Identification Test (AUDIT), Acute or chronic hepatitis C, Acute or chronic hepatitis B, Immunodeficiency acquired syndrome Pregnant women, In the last year, history of herbal consumption, total parenteral nutrition, amiodarone, methotrexate, hormonal contraceptives, steroids, tamoxifen, valproic acid or any other drug associated with the development of liver steatosis. Uncontrolled hypothyroidism or hyperthyroidism, Any uncontrolled chronic disease.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1: Placebo<br>Placebo | Other: placebo<br>* placebo tablets: 1 Tablet by mouth twice in day during 6 months<br>|
| Experimental: Group 2: Metadoxine<br>therapy with metadoxine | Drug: metadoxine<br>* metadoxine 500mg tablets: 1 Tablet by mouth twice in day during 6 months<br>* Other names: Abrixone, Metadoxil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement in the degree of non-alcoholic fatty liver disease score (NAS) | Non-alcoholic fatty liver disease score (NAS) is an histological classification to assessed the severity of liver steatosis, lobular inflammation and ballooning in the liver biopsy. It is measured on a scale from 0 to 8 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement in liver steatosis measured on a scale from 0 to 3 | Liver biopsy: measured on a scale from 0 to 3 | 6 months | 
| improvement in lobular inflammation measured on a scale from 0 to 3 | Liver biopsy: measured on a scale from 0 to 3 | 6 months | 
| improvement in ballooning measured on a scale from 0 to 2 | Liver biopsy: measured on a scale from 0 to 2 | 6 months | 
| improvement in alanine aminotransferase serum levels |  | 6 months | 
| improvement in aspartate aminotransferase serum levels |  | 6 months | 
| improvement in the degree of liver fibrosis measured on a scale from 0 to 2 | Liver biopsy: measured on a scale from 0 to 2 | 6 months | 
| to compare the occurrence of adverse effects between groups |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-alcoholic steatohepatitis, metadoxine, efficacy, therapy