A Novel Pharmacotherapy for Alcoholism and Alcohol Liver Disease
Alcohol use disorders in the United States (US) account for about 1 death every 5 minutes including 32% of all traffic fatalities, an average of one fatality related to alcohol every 39 minutes. Alcohol liver disease (ALD) is often present in alcohol dependent (AD) patients. Treatments for ALD have limited success when drinking continues. Cessation of alcohol consumption or a significant reduction in alcohol intake improves histology and survival of patients with any stage of ALD. While alcohol abstinence may not be sufficient to provide a total recovery of ALD, patients with uncomplicated ALD have a 5-year survival of almost 90% if they stop drinking. Consequently, abstinence is the most important therapeutic intervention for patients with ALD. When combined with psychosocial treatments, currently approved medications can improve outcomes for some AD individuals; however, these treatments are unsuccessful for many others. One of the limiting factors that must be taken into consideration when using currently approved medications such as disulfiram or naltrexone is liver function. Given their hepatic metabolism, disulfiram or naltrexone both increase the risk of hepatotoxicity in AD individuals. Therefore, a pharmacotherapy that is effective for AD, that is safe for the liver and able to recover alcohol-related liver damage thereby improving liver function, would be an ideal medication. However as of now, no drug has been found to provide all of these benefits to AD individuals. It is proposed therefore to test metadoxine (MTDX) that it is hypothesized is 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Novel Pharmacotherapy for Alcoholism and Alcohol Liver Disease|
- Percent Days Abstinent (PDA) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]We hypothesize that metadoxine (MTDX), compared to placebo significantly increases percent days abstinent (PDA) during the 12 weeks of drug administration, as measured by the timeline follow-back (TLFB).
- AST/ALT ratio [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]We hypothesize that MTDX, compared to placebo results in significant reduction in the AST/ALT ratio (a typical biomarker of alcoholic liver disease [ALD]) during the 12 weeks of drug administration.
- Follow-up PDA [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]We hypothesize that MTDX, compared to placebo results in significantly higher PDA from discontinuation of the medication to the 3-month follow-up, as measured by the TLFB.
- Adverse Events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]We hypothesize that MTDX, compared to placebo has no greater frequency and intensity of Adverse Events (AE).
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Metadoxine 500mg tablet t.i.d.for 12 weeks
Placebo Comparator: Sugar pill
Please refer to this study by its ClinicalTrials.gov identifier: NCT01504295
|Contact: Lorenzo Leggio, MD||401-863-6638|
|United States, Rhode Island|
|Brown University Center for Alcohol and Addiction Studies||Recruiting|
|Providence, Rhode Island, United States, 02912|
|Contact: Lorenzo Leggio, MD 401-863-6638|
|Principal Investigator: George A Kenna, PhD RPh|
|Principal Investigator: Lorenzo Leggio, MD,PhD, MS|
|Sub-Investigator: Robert M Swift, MD, PhD|
|Sub-Investigator: William H Zywiak, PhD|