A Novel Pharmacotherapy for Alcoholism and Alcohol Liver Disease

• Status: Completed
• Trial end date: 2015-02-01
• Target enrollment: 0
• Participant gender: All

Summary

It is proposed to test metadoxine (MTDX) that it is hypothesized to be significantly beneficial for the treatment of alcoholism and ALD. Metadoxine is currently approved in Europe for acute and chronic alcohol intoxication but has never been tested in the US. Furthermore, MTDX is used in Europe to treat ALD. Preliminary evidence shows that MTDX reduces alcohol consumption in AD individuals. If the role of MTDX in reducing alcohol consumption and improve liver function is confirmed by a rigorous study design, then MTDX might represent a truly innovative pharmacotherapy for AD, given the potential to be used for AD individuals with ALD. However until this proposal, MTDX has never been investigated as a treatment for AD able to reduce both alcohol consumption and improve alcohol-related liver damage via a double-blind placebo-controlled study. This project therefore proposes to conduct a 12-week (followed by a 3-month follow-up), double-blind, placebo-controlled, between-subject randomized clinical trial with MTDX (500mg t.i.d.) in AD individuals.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brown University
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Treatments: Metadoxine

Criteria

Inclusion Criteria:

• age ≥18;

• females must be post-menopausal for ≥1 year, surgically sterile, or practicing a birth control before entry and throughout the study; have a negative urine pregnancy test at screening and before randomization;

• current DSM-IV diagnosis of alcohol use disorder (or if relevant at study start-DSM-V) with current (i.e. past 90 days prior to screening) "at-risk" drinking defined as an average overall consumption of ≥28 drinks/week for men and ≥21 drinks/week for women;

• desire abstinence;

• evidence of alcoholic liver disease (ALD) based on a thorough history, physical examination, and laboratory tests (i.e. the De Ritis ratio of AST:ALT ratio ~2:1), which is characteristic of ALD.

Exclusion Criteria:

• lifetime DSM diagnosis of schizophrenia, bipolar disorder, or other psychosis;

• in the investigators' opinion, risk of suicide (e.g. active plan, or recent attempt in last year);

• current DSM-IV diagnosis of dependence on any psychoactive substance other than alcohol and nicotine;

• repeated positive urine screen for any substance other than marijuana;

• history of hospitalization for alcohol intoxication delirium or alcohol withdrawal delirium;

• Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) score >10, at any assessment;

• having received a psychological and/or pharmacological treatment for alcohol or having participated in a treatment research study within the past 90 days;

• having participated in any clinical trial with an investigational agent within the past 30 days;

• treatment with levodopa/carbidopa or reported diagnosis of Parkinson's disease;

• AST and/or ALT >10 x upper normal limit; Child-Pugh-Turcotte (CPT) score stage C, model for end-stage liver disease (MELD) score >21 (CPT and MELD scores are assessed by blood tests - e.g. bilirubin, albumin, INR, Cr - and medical history); and/or medical history positive for decompensated liver disease (ascites, encephalopathy, variceal bleeding or hepatorenal syndrome) and/or medical history positive for hepatocellular carcinoma; 11) history of allergy to MTDX or PCA and pyridoxol;

• other serious illnesses, e.g. kidney failure.