Genetic and Brain Mechanisms of Naltrexone's Treatment Efficacy for Alcoholism

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Medical University of South Carolina
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Raymond F. Anton, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT00920829
First received: June 11, 2009
Last updated: October 24, 2013
Last verified: October 2013
  Purpose

The overarching aim of this trial is to evaluate naltrexone's efficacy in light of genetic variation and brain response to alcohol cues utilizing a neuroimaging paradigm. This trial has four specific aims. First, this trial will evaluate whether the presence of the OPRM1 Asp40 allele substitution is associated with improved treatment response to naltrexone in treatment-seeking alcoholics. Second, it will evaluate whether there is a difference in the naltrexone dampening of the alcohol cue-induced brain activation dependent on OPRM1 genotype. Third, it will explore whether alcohol cue-induced brain activation dampening by naltrexone might be a mediating factor in the treatment effects of naltrexone, the OPRM1 gene, or their interaction that might be observed in the first aim. Finally, this trial will evaluate the effect of medication compliance, or adverse effects, on the observed medication by genotype treatment response. A secondary aim will measure medication compliance and side effects based on OPRM1 genotype.


Condition Intervention Phase
Alcohol Dependence
Drug: Drug
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Genetic and Brain Mechanisms of Naltrexone?s Treatment Efficacy for Alcoholism

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • percent heavy drinking days by mu opitate receptor gene [ Time Frame: 16-week treatment period ] [ Designated as safety issue: No ]
  • adverse effects by mu opiate receptor gene [ Time Frame: 16 week trial ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • drinks per drinking day based by mu opiate receptor gene [ Time Frame: 16 week trial ] [ Designated as safety issue: No ]
  • percent days abstinent by mu opiate receptor gene [ Time Frame: 16 week trial ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: June 2009
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Naltrexone Drug: Drug
Naltrexone 25 or 50 mg per tiration schedule
Placebo Comparator: Placebo Drug: Placebo
placebo

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Age 18 70
  2. Subjects will meet criteria for primary alcohol dependence
  3. Consumes, on average, at least 5 standard drinks per day for men and 4 drinks per day for women in the 90 days pre-screening. Has at least 50% of days as heavy drinking days (as defined above).
  4. Able to maintain sobriety for four days (with or without the aid of alcohol detoxification medications) as determined by self report and breathalyzer measurements
  5. Able to read and understand questionnaires and informed consent
  6. Lives within approximately 50 miles of the study site

Exclusion Criteria

  1. Currently meets DSM IV criteria for any other psychoactive substance dependence disorder except nicotine dependence
  2. Any psychoactive substance abuse, except marijuana, nicotine, and cocaine, within the last 30 days as evidenced by subject report, collateral report, or urine drug screen. May meet cocaine abuse criteria, but not dependence, and also must have two sequential urines free of illicit substances
  3. Meets DSM IV criteria for current and active axis I disorders of major depression, panic disorder, obsessive compulsive disorder, post traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder
  4. Meets DSM IV current criteria for dissociative disorder or eating disorders
  5. Has current suicidal ideation or homicidal ideation
  6. Need for maintenance or acute treatment with any psychoactive medication, except a stable dose (at least one month) of antidepressants
  7. Need for maintenance on anti-seizure medications (including topiramate and gabapentin)
  8. Use of disulfiram, acamprosate, or naltrexone in the last two weeks
  9. Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit medication ingestion
  10. Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at least 3.0 times normal at screening and/or after 5 days abstinence
  11. Sexually active female of child-bearing potential who is pregnant (by urine HCG), nursing, or who is not willing to use a reliable form of birth control
  12. Has current charges pending for a violent crime (not including DUI-related offenses)
  13. Does not have a stable living situation
  14. African American heritage due to low prevalence of Asp40 (also see Inclusion of Women and Minorities section)

Exclusion Criteria of fMRI Procedure

  1. Having metal objects in the body that are deemed unsafe in the MRI environment.
  2. Severe claustrophobia that cannot be managed with support and encouragement.
  3. Morbid obesity such that placement in the MRI scanner is impossible.
  4. History of significant head injury leading to unconsciousness.
  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: NCT00920829

Contacts
Contact: Konstantin Voronin, MD, PhD 843-792-4887 voronin@musc.edu
Contact: Patricia K Latham, Ph.D. 843-792-1230 lathampk@musc.edu

Locations
United States, South Carolina
Medical University of South Carolina, Center for Drug and Alcohol Programs Recruiting
Charleston, South Carolina, United States, 29425
Contact: Konstantin E Voronin, MD, Ph.D    843-792-2727    voronin@musc.edu   
Contact: Patricia K Latham, PhD, RN    843-792-1230    lathampk@musc.edu   
Principal Investigator: Raymond F Anton, MD         
Medical University of South Carolin Completed
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Medical University of South Carolina
Investigators
Principal Investigator: Raymond F Anton, MD Medical University of South Carolina
  More Information

No publications provided

Responsible Party: Raymond F. Anton, Distinguished University Professor, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT00920829     History of Changes
Other Study ID Numbers: ANTON-1R01AA017633-01A1, R01AA017633, 1R01AA017633-01A1
Study First Received: June 11, 2009
Last Updated: October 24, 2013
Health Authority: United States: Federal Government

Keywords provided by Medical University of South Carolina:
Alcohol Dependence
Alcoholism
Naltrexone
Substance Abuse
Genetics

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Naltrexone
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014