Acamprosate: Genes Associated With Response (ACAM)

This study has been completed.
Sponsor:
Collaborator:
Samuel C. Johnson Foundation
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00662571
First received: April 14, 2008
Last updated: March 20, 2013
Last verified: March 2013
  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 4

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: A Probe Study of Acamprosate: Genes Associated With Response

Resource links provided by NLM:


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

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


Enrollment: 485
Study Start Date: May 2008
Study Completion Date: February 2013
Primary Completion Date: February 2013 (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
Other Name: Campral is the brand name of 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.

  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:

  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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Minnesota
Mayo Clinic
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: David Mrazek, M.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00662571     History of Changes
Other Study ID Numbers: 07-007204, P20-acam
Study First Received: April 14, 2008
Last Updated: March 20, 2013
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:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
N-Methylaspartate
Acamprosate
Excitatory Amino Acid Agonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Alcohol Deterrents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014