Acamprosate: Genes Associated With Response

Alcoholism Clinical Trial

— ACAM  

Official title:

A Probe Study of Acamprosate: Genes Associated With Response

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00662571
• Other study ID #: 07-007204
• Secondary ID: P20-acam
• Status: Completed
• Phase: Phase 4
• First received: April 14, 2008
• Last updated: March 20, 2013
• Start date: May 2008
• Est. completion date: February 2013

Study information

• Verified date: March 2013
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 485
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Male or females, Age 18-80.

2. 2. 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).

3. Prior enrollment in the IRB approved protocol "Developing a DNA Repository for Genomic Studies of Addiction: A Pilot Study".

Exclusion Criteria:

1. Inability to provide informed consent.

2. Inability to speak English.

3. History of hypersensitivity or allergic reaction to acamprosate.

4. Moderate to severe renal impairment, as determined by a creatinine level > 1.5 mg/dL.

5. Diagnosis of primary biliary cirrhosis, chronic active hepatitis, and drug-induced hepatic insufficiency, as noted in the medical record.

6. Women who are pregnant, lactating, or are planning to become pregnant during the next year.

7. Any unstable active medical or additional psychiatric condition as determined by the investigator.

9. Active suicidal ideation as determined by responses provided during PRISM or as determined by the investigator.

Study Design

Observational Model: Case Control, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Alcoholism

Intervention

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

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	Samuel C. Johnson Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aim 1: To determine the relationship between genetically determined variation in the NMDA receptor and treatment response to acamprosate.		6 months	No
Secondary	Aim 2: To determine the relationship between genetically determined variation in the mGluR5 receptor and treatment response to acamprosate.		6months	No