Effectiveness of Naltrexone Versus Placebo to Reduce Craving for Alcohol With Evaluation of Genetic Variability.

NCT ID: NCT00366626

Last Updated: 2017-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2010-01-31

Brief Summary

The purpose of this study is to determine whether naltrexone (an opiate blocking agent approved for the treatment of alcohol dependence) is more effective in the reduction of alcohol craving and drinking compared to placebo in individuals with particular genetic predisposition.

Detailed Description

About 300 non-treatment seeking alcoholics will be recruited through advertisement and paid for their participation. They will be assessed, subtyped for mu-opiate receptor and catechol-O-methyltransferase (COMT) allelic variants and 88 individuals (44 with the more common AA gene and 44 with either an AG or GG gene) will be randomly assigned to take either naltrexone (50 mg/day) or a matching placebo for 7 days. Since the val and met alleles of the catechol-O-methyltransferase (COMT) gene are each present in about 50% of the population they will be equally distributed by urn randomization to all opiate allele and treatment groups. After 5 days of natural drinking and one day of abstinence, subjects will undergo an alcohol cue-induced brain activity scan using well-established fMRI techniques on Day 6 of study drug. The following day all subjects will receive a standard dose (gender and weight corrected) of alcohol and be evaluated for alcohol reactivity (stimulation, sedation, intoxication, craving) over 40 minutes. They then will be allowed to consume up to 8 mini-drinks over a 2-hour period. Afterwards all subjects will receive educational/motivational counseling regarding their alcohol use and its effects. Referral for treatment will be offered.

Conditions

Alcohol Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1.

Naltrexone one capsule a day

Group Type: EXPERIMENTAL

Naltrexone

Intervention Type: DRUG

Naltrexone (25 mg/day for days 1-2 and 50 mg/day for days 3-7)

2

One capsule a day match to naltrexone

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo for 7 days matched to Naltrexone

Interventions

Naltrexone

Naltrexone (25 mg/day for days 1-2 and 50 mg/day for days 3-7)

Intervention Type: DRUG

Placebo

Placebo for 7 days matched to Naltrexone

Intervention Type: DRUG

Other Intervention Names

ReVia

Eligibility Criteria

Inclusion Criteria

• 1. Age 21-65. 2. Meets the DSM IV criterion for current alcohol dependence including "loss of control over drinking" (criterion 4) but does not necessarily have signs of physiologic dependence as expressed in criterion for tolerance development (criterion 1) and withdrawal symptoms or use to avoid withdrawal symptoms (criterion 2).

3. Drinks hard liquor/spirits and does not have aversion to this form of alcohol.

4. Drinks alone (not in the presence of others) some of the time (to maximize the potential of drinking in the bar lab where a subject will not be in the company of others).

5. Currently is not engaged in, and does not want treatment for, alcohol related problems.

6. Able to read and understand questionnaires and informed consent. 7. Lives within 50 miles of the study site. 8. Able to maintain abstinence for two days (without the aid of detox medications) as determined by self-report and breathalyzer measurements.

Inclusion for fMRI imaging sub-study (see methodology section for rationale):

1. Does not have metal objects in the head/neck.

2. Does not have a history of claustrophobia leading to significant clinical anxiety symptoms.

Exclusion Criteria

• 1. Currently meets DSM-IV criteria for any other psychoactive substance dependence disorder.

2. History of opiate abuse or a positive urine drug screen for opiates. 3. Any psychoactive substance use (except marijuana and nicotine) within the last 30 days as evidenced by self-report and urine drug screen. For marijuana - no use within the last seven days.

4. Meets DSM-IV criteria for current axis I disorders of major depression, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, bipolar affective disorder, schizophrenia, dissociative disorders and eating disorders, any other psychotic disorder or an organic mental disorder.

5. Has current suicidal ideation or homicidal ideation. 6. Need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications.

7. Current use of disulfiram, naltrexone, or acamprosate. 8. Clinically significant medical problems such as, cardiovascular, renal, gastrointestinal, or endocrine problems that would impair participation or limit medication ingestion.

9. Past history of alcohol related medical illness such as gastrointestinal bleeding, pancreatitis, peptic ulcer, hepatic cirrhosis or alcoholic hepatitis.

10. Hepatocellular disease indicated by elevations of SGPT Alanine transaminase(ALT) or SGOT Aspartate transaminase(AST) greater than 3 times normal at screening.

11. Females of child-bearing potential who are pregnant (by urine HCG), nursing, or who are not using 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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raymond F Anton, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

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

Charleston, South Carolina, United States

Countries

United States

References

Anton RF, Voronin KK, Randall PK, Myrick H, Tiffany A. Naltrexone modification of drinking effects in a subacute treatment and bar-lab paradigm: influence of OPRM1 and dopamine transporter (SLC6A3) genes. Alcohol Clin Exp Res. 2012 Nov;36(11):2000-7. doi: 10.1111/j.1530-0277.2012.01807.x. Epub 2012 May 2.

Reference Type: DERIVED

PMID: 22551036 (View on PubMed)

Other Identifiers

P50AA010761

Identifier Type: NIH

Identifier Source: org_study_id

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