NCT01504295

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Apr 2012

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 4, 2012

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 5, 2012

Completed
3 months until next milestone

Study Start

First participant enrolled

April 1, 2012

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2015

Completed
Last Updated

July 22, 2015

Status Verified

July 1, 2015

Enrollment Period

2.8 years

First QC Date

January 4, 2012

Last Update Submit

July 20, 2015

Conditions

Alcoholism,Alcoholic Liver Disease

Outcome Measures

Primary Outcomes (1)

  • Percent Days Abstinent (PDA)

    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).

    12 weeks

Secondary Outcomes (2)

  • Follow-up PDA

    12 weeks

  • Adverse Events

    12 weeks

Study Arms (2)

Metadoxine

EXPERIMENTAL

Metadoxine 500mg tablet t.i.d.for 12 weeks

Drug: Metadoxine

Sugar pill

PLACEBO COMPARATOR

Placebo group

Drug: Metadoxine

Interventions

MetadoxineDRUG

Improve Liver Function and Reduce ALcohol Use

MetadoxineSugar pill

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Brown University Center for Alcohol and Addiction Studies

Providence, Rhode Island, 02912, United States

Location

Related Publications (5)

  • Shpilenya LS, Muzychenko AP, Gasbarrini G, Addolorato G. Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study. Alcohol Clin Exp Res. 2002 Mar;26(3):340-6.

    PMID: 11923586BACKGROUND

  • Addolorato G, Ancona C, Capristo E, Gasbarrini G. Metadoxine in the treatment of acute and chronic alcoholism: a review. Int J Immunopathol Pharmacol. 2003 Sep-Dec;16(3):207-14. doi: 10.1177/039463200301600304.

    PMID: 14611722BACKGROUND

  • Leggio L, Kenna GA, Ferrulli A, Zywiak WH, Caputo F, Swift RM, Addolorato G. Preliminary findings on the use of metadoxine for the treatment of alcohol dependence and alcoholic liver disease. Hum Psychopharmacol. 2011 Dec;26(8):554-9. doi: 10.1002/hup.1244. Epub 2011 Nov 16.

    PMID: 22095793BACKGROUND

  • Guerrini I, Gentili C, Nelli G, Guazzelli M. A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence. Subst Abuse Treat Prev Policy. 2006 Dec 18;1:35. doi: 10.1186/1747-597X-1-35.

    PMID: 17176456BACKGROUND

  • Caballeria J, Pares A, Bru C, Mercader J, Garcia Plaza A, Caballeria L, Clemente G, Rodrigo L, Rodes J. Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty Liver. J Hepatol. 1998 Jan;28(1):54-60. doi: 10.1016/s0168-8278(98)80202-x.

    PMID: 9537864BACKGROUND

MeSH Terms

Conditions

AlcoholismLiver Diseases, Alcoholic

Interventions

metadoxine

Condition Hierarchy (Ancestors)

Alcohol-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental DisordersLiver DiseasesDigestive System DiseasesAlcohol-Induced Disorders

Study Officials

  • George A Kenna, PhD RPh

    Brown University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Psychiatry

Study Record Dates

First Submitted

January 4, 2012

First Posted

January 5, 2012

Study Start

April 1, 2012

Primary Completion

January 1, 2015

Study Completion

February 1, 2015

Last Updated

July 22, 2015

Record last verified: 2015-07

Locations

US(1)