ACAM: Acamprosate: Genes Associated With Response

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT00662571

Collaborator

Samuel C. Johnson Foundation (Other)

485

Enrollment

Location

57.1

Duration (Months)

8.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In 2004, acamprosate was approved in the U.S. for abstinence maintenance, by decreasing craving, in alcoholic patients who have undergone detoxification. while a new anti-craving drug was encouraging, only 36.1% of the subjects treated with acamprosate remained abstinent for 6 months. Having the ability to identify treatment responsive individuals would have a major impact on the use of acamprosate.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism	Drug: acamprosate

Detailed Description

The primary objective of this pharmacogenomic probe study of acamprosate is to identify genetic variations that predict response. Our hypothesis is that effective acamprosate response in alcohol dependent subjects may be influenced by genetically controlled variation in the functionality of the N-methyl-D-aspartate receptor (NMDA) and/or the type 5 metabotropic glutamate receptor (mGluR5). Hypothesis confirmation could lead to development of effective individualized treatment recommendations for alcohol dependent patients based on pharmacogenomically relevant genetic variations.

The general goal is to identify genetic polymorphic variants that differentiate subjects continuously abstinent for six months while taking acamprosate from relapsed subjects. The initial analysis will determine whether any of ten polymorphisms in four target genes (GRIN1, GRIN2A and GRIN2B that code for the NMDA receptor and GRM5 that codes for the type mGluR5 receptor) are associated with successful abstinence. Subsequent analyses will examine whether variation in a comprehensive set of 383 linkage disequilibrium haplotype tagged single nucleotide polymorphisms of these four genes predicts successfully abstinent subjects.

Study Design

Study Type:

Observational

Actual Enrollment :

485 participants

Observational Model:

Case-Control

Time Perspective:

Retrospective

Official Title:

A Probe Study of Acamprosate: Genes Associated With Response

Study Start Date :

May 1, 2008

Actual Primary Completion Date :

Feb 1, 2013

Actual Study Completion Date :

Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
A Our hypothesis is that effective acamprosate response in alcohol dependent subjects may be influenced by genetically controlled variation in the functionality of the N-methyl-D-aspartate receptor (NMDA) and/or the type 5 metabotropic glutamate receptor (mGluR5). Hypothesis confirmation could lead to development of effective individualized treatment recommendations for alcohol dependent patients based on pharmacogenomically relevant genetic variations. There will be no placebo drug given. Just measurement of genetic response.	Drug: acamprosate acamprosate 333mg tabs, 2tabs 3times per day = 1998mg/day Other Names: Campral is the brand name of acamprosate.

Arm

Intervention/Treatment

Our hypothesis is that effective acamprosate response in alcohol dependent subjects may be influenced by genetically controlled variation in the functionality of the N-methyl-D-aspartate receptor (NMDA) and/or the type 5 metabotropic glutamate receptor (mGluR5). Hypothesis confirmation could lead to development of effective individualized treatment recommendations for alcohol dependent patients based on pharmacogenomically relevant genetic variations. There will be no placebo drug given. Just measurement of genetic response.

Drug: acamprosate

acamprosate 333mg tabs, 2tabs 3times per day = 1998mg/day

Other Names:

Campral is the brand name of acamprosate.

Outcome Measures

Primary Outcome Measures

Aim 1: To determine the relationship between genetically determined variation in the NMDA receptor and treatment response to acamprosate. [6 months]

Secondary Outcome Measures

Aim 2: To determine the relationship between genetically determined variation in the mGluR5 receptor and treatment response to acamprosate. [6months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or females, Age 18-80.
1. Primary diagnosis of alcohol dependence based on DSM-IV-TR criteria and determined by the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) (stable mood and anxiety disorders will not be exclusionary).
Prior enrollment in the IRB approved protocol "Developing a DNA Repository for Genomic Studies of Addiction: A Pilot Study".

Exclusion Criteria:

Inability to provide informed consent.
Inability to speak English.
History of hypersensitivity or allergic reaction to acamprosate.
Moderate to severe renal impairment, as determined by a creatinine level > 1.5 mg/dL.
Diagnosis of primary biliary cirrhosis, chronic active hepatitis, and drug-induced hepatic insufficiency, as noted in the medical record.
Women who are pregnant, lactating, or are planning to become pregnant during the next year.
Any unstable active medical or additional psychiatric condition as determined by the investigator.
Active suicidal ideation as determined by responses provided during PRISM or as determined by the investigator.