Clinical trial NCT02541045: Clinical Trial to Evaluate the Efficacy of Metadoxine as a Therapy for Patients With Non-alcoholic Steatohepatitis
Official title: Clinical Trial to Evaluate the Efficacy of Metadoxine as a Therapy for Patients With Non-alcoholic Steatohepatitis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Non-alcoholic Steatohepatitis
Keywords: non-alcoholic steatohepatitis
metadoxine
efficacy
therapy
Lead sponsor: Hospital General de Mexico
Sponsor class: OTHER_GOV
First posted: 2015-09-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: improvement in the degree of non-alcoholic fatty liver disease score (NAS)
timeFrame: 6 months
Secondary outcomes:
measure: improvement in liver steatosis measured on a scale from 0 to 3
timeFrame: 6 months
measure: improvement in lobular inflammation measured on a scale from 0 to 3
timeFrame: 6 months
measure: improvement in ballooning measured on a scale from 0 to 2
timeFrame: 6 months
measure: improvement in alanine aminotransferase serum levels
timeFrame: 6 months
measure: improvement in aspartate aminotransferase serum levels
timeFrame: 6 months
measure: improvement in the degree of liver fibrosis measured on a scale from 0 to 2
timeFrame: 6 months
measure: to compare the occurrence of adverse effects between groups
timeFrame: 6 months
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Hospital General de México
state: DF
Study officials:
affiliation: Hospital General de México
name: Fatima Higuera-de la Tijera, MD, MSc.
role: STUDY_DIRECTOR
References: