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

• ClinicalTrials.gov Identifier: NCT00920829
• Recruitment Status: Completed
• First Posted: June 15, 2009
• Results First Posted: June 4, 2018
• Last Update Posted: July 10, 2018
• Sponsor: Medical University of South Carolina
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Information provided by (Responsible Party): Medical University of South Carolina

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Alcohol Dependence	Drug: Naltrexone 50 Mg; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 358 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Genetic and Brain Mechanisms of Naltrexone?s Treatment Efficacy for Alcoholism
• Study Start Date: June 2009
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: A118G A/A with Naltrexone; Individuals with the OPRM1 genotype Asn40 are given naltrexone 50 mg after 2 days at 25 mg for 16 weeks with Medication Management 9 visits in 16 weeks	Drug: Naltrexone 50 Mg; Naltrexone 25 or 50 mg per titration schedule
Placebo Comparator: A118G A/A with Placebo; Individuals with the OPRM1 genotype Asn40 are given Placebo for 16 weeks with Medication Management in 16 weeks	Drug: Placebo; placebo
Active Comparator: A118G Any G with Naltrexone; Individuals with the OPRM1 genotype Any G (Asp) are given naltrexone 50 mg after 2 days of naltrexone 25 mg for 16 weeks with Medication Management 9 visits in 16 weeks	Drug: Naltrexone 50 Mg; Naltrexone 25 or 50 mg per titration schedule
Placebo Comparator: A118G Any G with Placebo; Individuals with the OPRM1 genotype Any G (Asp) are given 50 mg naltrexone after 2 days at 25 mg for 16 weeks with Medication Management 9 visits in 16 weeks	Drug: Placebo; placebo

Outcome Measures

Primary Outcome Measures :

1. Percent Heavy Drinking Days by mu Opioid Receptor Gene [ Time Frame: Time Line Follow-Back drinking collected at each of 9 visits (weeks 1, 2, 3, 4, 6, 8, 10, 12 and 16) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, South Carolina

Medical University of South Carolina, Center for Drug and Alcohol Programs

Charleston, South Carolina, United States, 29425

Medical University of South Carolin

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Medical University of South Carolina

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Raymond F Anton, MD; Medical University of South Carolina

More Information

Additional Information:

Predictors of Naltrexone Response in a Randomized Trial: Reward-Related Brain Activation, OPRM1 Genotype, and Smoking Status. 

Publications of Results:

Schacht JP, Randall PK, Latham PK, Voronin KE, Book SW, Myrick H, Anton RF. Predictors of Naltrexone Response in a Randomized Trial: Reward-Related Brain Activation, OPRM1 Genotype, and Smoking Status. Neuropsychopharmacology. 2017 Dec;42(13):2640-2653. doi: 10.1038/npp.2017.74. Epub 2017 Apr 14. Erratum in: Neuropsychopharmacology. 2017 Dec;42(13):2654.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00920829
• Other Study ID Numbers: ANTON-1R01AA017633-01A1
• First Posted: June 15, 2009
• Results First Posted: June 4, 2018
• Last Update Posted: July 10, 2018
• Last Verified: June 2018

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; Alcohol Deterrents; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents