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

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

Study Overview

• Status: Withdrawn
• Conditions: Non-alcoholic Steatohepatitis
• Intervention / Treatment: Other: placebo; Drug: metadoxine

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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • DF
    • Mexico City, DF, Mexico, 06726
      • Hospital General de Mexico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital General de Mexico
• Investigators: Study Director: Fatima Higuera-de la Tijera, MD, MSc., Hospital General de Mexico

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): March 1, 2024
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: August 31, 2015
• First Submitted That Met QC Criteria: September 1, 2015
• First Posted (Estimated): September 4, 2015

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: efficacy; non-alcoholic steatohepatitis; therapy; metadoxine
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Alcohol Deterrents; Metadoxine
• Other Study ID Numbers: DI/15/108/03/48