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

Phase 3
Withdrawn
Conditions
Non-alcoholic Steatohepatitis
Interventions
Other: placebo
Registration Number
NCT02541045
Lead Sponsor
Hospital General de Mexico
Brief Summary

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

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.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 1: PlaceboplaceboPlacebo
Group 2: Metadoxinemetadoxinetherapy with metadoxine
Primary Outcome Measures
NameTimeMethod
improvement in the degree of non-alcoholic fatty liver disease score (NAS)6 months

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

Secondary Outcome Measures
NameTimeMethod
to compare the occurrence of adverse effects between groups6 months
improvement in alanine aminotransferase serum levels6 months
improvement in aspartate aminotransferase serum levels6 months
improvement in lobular inflammation measured on a scale from 0 to 36 months

Liver biopsy: measured on a scale from 0 to 3

improvement in ballooning measured on a scale from 0 to 26 months

Liver biopsy: measured on a scale from 0 to 2

improvement in liver steatosis measured on a scale from 0 to 36 months

Liver biopsy: measured on a scale from 0 to 3

improvement in the degree of liver fibrosis measured on a scale from 0 to 26 months

Liver biopsy: measured on a scale from 0 to 2

Trial Locations

Locations (1)

Hospital General de México

🇲🇽

Mexico City, DF, Mexico

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