Acamprosate: Genes Associated With Response - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	Samuel C. Johnson Foundation
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00662571

Purpose

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	Intervention	Phase
Alcoholism	Drug: acamprosate	Phase IV

Study Type:	Observational
Study Design:	Case Control, Retrospective
Official Title:	A Pilot Probe Study of Acamprosate: Genes Associated With Response

Resource links provided by NLM:

MedlinePlus related topics: Alcoholism

Drug Information available for: Acamprosate calcium Acamprosate

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:

Aim 1: To determine the relationship between genetically determined variation in the NMDA receptor and treatment response to acamprosate. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Aim 2: To determine the relationship between genetically determined variation in the mGluR5 receptor and treatment response to acamprosate. [ Time Frame: 6months ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Samples obtained from study "Developing a DNA Repository for Genomic Studies of Addiction: A Pilot Study"

Estimated Enrollment:	200
Study Start Date:	May 2008
Estimated Study Completion Date:	April 2012
Estimated Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
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

Groups/Cohorts

Assigned Interventions

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

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Subjects selected from Mayo Clinics Addiction programs.

Criteria

Inclusion Criteria:

Male or females, Age 18-80.
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).
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.

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00662571

Contacts

Contact: David Mrazek, M.D.	507-255-9412	mrazek.david@mayo.edu
Contact: Mark Frye, M.D.	507-255-9412	frye.mark@mayo.edu

Locations

United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

Samuel C. Johnson Foundation

Investigators

Principal Investigator:

David Mrazek, M.D.

Mayo Clinic, Department of Psychiatry

More Information

No publications provided

Responsible Party:	Mayo Clinic ( David Mrazek, M.D. )
Study ID Numbers:	07-007204, P20-acam
Study First Received:	April 14, 2008
Last Updated:	October 13, 2009
ClinicalTrials.gov Identifier:	NCT00662571 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Mayo Clinic:

nucleotide polymorphisms
disequilibrium haplotype
acamprosate
differentiate
pharmacogenomic
effective individualized treatment

alcohol dependent
N-methyl-D-aspartate receptor (NMDA)
metabotropic glutamate receptor
decreasing craving
abstinence maintenance

Additional relevant MeSH terms:

Mental Disorders
Therapeutic Uses
Alcoholism
Substance-Related Disorders
Disorders of Environmental Origin

Alcohol-Related Disorders
Central Nervous System Agents
Pharmacologic Actions
Alcohol Deterrents
Acamprosate

ClinicalTrials.gov processed this record on November 27, 2009