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

NCT00920829 | Completed Phase 4 Results DMC

• 1 other identifier: ANTON-1R01AA017633-01A1
• Study Type: interventional
• Target: 358
• Locations: 1 country
• Sites: 2

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.

Conditions

Alcohol Dependence

Keywords

Alcohol Dependence; Alcoholism; Naltrexone; Substance Abuse; Genetics

Outcome Measures

Primary Outcomes (1)

• Percent Heavy Drinking Days by mu Opioid Receptor Gene

  Time Line Follow-Back drinking collected at each of 9 visits (weeks 1, 2, 3, 4, 6, 8, 10, 12 and 16)

Study Arms (4)

A118G A/A with Naltrexone

ACTIVE COMPARATOR

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

A118G A/A with Placebo

PLACEBO COMPARATOR

Individuals with the OPRM1 genotype Asn40 are given Placebo for 16 weeks with Medication Management in 16 weeks

Drug: Placebo

A118G Any G with Naltrexone

ACTIVE COMPARATOR

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

A118G Any G with Placebo

PLACEBO COMPARATOR

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

Interventions

Naltrexone 50 Mg DRUG

Naltrexone 25 or 50 mg per titration schedule

A118G A/A with Naltrexone; A118G Any G with Naltrexone

Placebo DRUG

placebo

A118G A/A with Placebo; A118G Any G with Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 70
• Subjects will meet criteria for primary alcohol dependence
• 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).
• Able to maintain sobriety for four days (with or without the aid of alcohol detoxification medications) as determined by self report and breathalyzer measurements
• Able to read and understand questionnaires and informed consent
• Lives within approximately 50 miles of the study site

You may not qualify if:

• Currently meets DSM IV criteria for any other psychoactive substance dependence disorder except nicotine dependence
• 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
• 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
• Meets DSM IV current criteria for dissociative disorder or eating disorders
• Has current suicidal ideation or homicidal ideation
• Need for maintenance or acute treatment with any psychoactive medication, except a stable dose (at least one month) of antidepressants
• Need for maintenance on anti-seizure medications (including topiramate and gabapentin)
• Use of disulfiram, acamprosate, or naltrexone in the last two weeks
• Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit medication ingestion
• 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
• 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
• Has current charges pending for a violent crime (not including DUI-related offenses)
• Does not have a stable living situation
• Having metal objects in the body that are deemed unsafe in the MRI environment.
• Severe claustrophobia that cannot be managed with support and encouragement.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (2)

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

Charleston, South Carolina, 29425, United States

Location

Medical University of South Carolin

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• 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.

  PMID: 28409564 RESULT

Related Links

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

MeSH Terms

Conditions

Alcoholism; Substance-Related Disorders

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Raymond Anton
• Organization: Medical University of South Carolina

antonr@musc.edu

843-792-1226

Study Officials

• Raymond F Anton, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2009
• First Posted: June 15, 2009
• Study Start: June 1, 2009
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: July 10, 2018
• Results First Posted: June 4, 2018

Record last verified: 2018-06

Locations

US (2)