Safety of Acamprosate for Alcohol Dependence in the Elderly: An Open-Label Study (SAFADIE)

Summary

Alcohol abuse and dependence are very prevalent and result in significant morbidity, mortality and cost to society (Harwood 2000). Pharmacotherapies to assist with alcohol dependence consist of disulfiram, naltrexone and acamprosate. Of these, acamprosate is unique in that it is not metabolized by the liver, but rather completely excreted renally. In contrast, naltrexone is metabolized by the CYP450 system of the liver and less than 2% is excreted unchanged and can cause liver damage (PDR 2005). Multiple cases of hepatitis, including both cholestatic and fulminant hepatitis, as well as hepatic failure resulting in transplantation or death, have been reported with administration of disulfiram (PDR 2005). The incidence of liver disease among alcoholics is high and increases with age and years of drinking and this may preclude the use of antabuse or naltrexone to help alcohol dependent patients with liver disease or that are elderly . Thus acamprosate has a unique safety profile that would make it ideally suited for treating alcohol dependence in the elderly, even in the presence of hepatic impairment. The current study is to evaluate the safety profile of acamprosate in elderly patients with alcohol dependence.

Acamprosate, calcium acetyl homotaurinate, has been approved in most European countries and the U.S. for the maintenance of abstinence in recently detoxified alcoholics. The mechanism of action involves primarily the restoration of a normal N-methyl- D -aspartate (NMDA) receptor tone in glutamatergic systems (Rammes et al 2001). Several trials of acamprosate confirm its efficacy in the maintenance of abstinence in alcohol dependence (Lesch et al. 2001; Slattery et al. 2003; Mann et al. 2004; Verheul et al. 2004). It also reduces the severity of relapse in alcoholics in abstinence based treatment programs (Chick et al. 2003). There is limited data on the safety of acamprosate in the elderly (PDR 2005).

For the purposes of this study, elderly will be defined as 60 years or older.

STUDY OBJECTIVE: To determine the short-term safety of Acamprosate in the treatment of alcohol dependence in the elderly.

Conditions

• Alcohol Dependence

Interventions

DRUG

Acamprosate (Campral)

During the course of the study patients will be supplied with 333mg tablets of acamprosate provided by the Sponsor. The study medication will be administered at a dose of 666mg (=two tablets) three times a day for patients with a creatinine clearance \>50. The dose will be 333mg three times a day for patients with a creatinine clearance in the range of 30-50. Treatment compliance will be monitored by counts of returned medication. Records of all concomitant medications will be taken at each study visit as well as reports of adverse events (as shown above).

DRUG

Acamprosate

During the course of the study patients will be supplied with 333mg tablets of acamprosate provided by the Sponsor. The study medication will be administered at a dose of 666mg (=two tablets) three times a day for patients with a creatinine clearance \>50. The dose will be 333mg three times a day for patients with a creatinine clearance in the range of 30-50.

Sponsors & Collaborators

• University of New Mexico

  lead OTHER

Principal Investigators

• Florian Birkmayer, M.D. · University of New Mexico, Department of Psychiatry

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-12-31

Primary Completion

2006-12-31

Completion

2006-12-31

Countries

• United States

Study Locations