Acamprosate: Genes Associated With Response
Information source: Mayo Clinic
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Alcoholism
Intervention: acamprosate (Drug)
Phase: Phase 4
Status: Not yet recruiting
Sponsored by: Mayo Clinic Official(s) and/or principal investigator(s):
David Mrazek, M.D., Principal Investigator, Affiliation: Mayo Clinic, Department of Psychiatry
Overall contact:
David Mrazek, M.D., Phone: 507-255-9412, Email: mrazek.david@mayo.edu
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.
Clinical Details
Official title: A Pilot Probe Study of Acamprosate: Genes Associated With Response
Study design: Screening, Non-Randomized, Open Label, Single Group Assignment, Pharmacokinetics/Dynamics Study
Primary outcome: Aim 1: To determine the relationship between genetically determined variation in the NMDA receptor and treatment response to acamprosate.
Secondary outcome: Aim 2: To determine the relationship between genetically determined variation in the mGluR5 receptor and treatment response to 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
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Male or females, Age 18-65.
2. 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.
8. Diagnosis of active substance dependence other than alcohol (i. e.: cannabis, caffeine,
prescription use of barbiturates, benzodiazepines, opiates, or stimulants) according
to DSM-IV-TR criteria as determined by the PRISM (nicotine is not exclusionary).
9. Active suicidal ideation as determined by responses provided during PRISM or as
determined by the investigator.
Locations and Contacts
David Mrazek, M.D., Phone: 507-255-9412, Email: mrazek.david@mayo.edu
Mayo Clinic, Rochester, Minnesota 55905, United States
Additional Information
Starting date: May 2008
Ending date: April 2012
Last updated: April 18, 2008
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