An Exploratory Study of Naltrexone Plus Aripiprazole for Alcohol Dependence (NALAPZ)

The principal aim of this exploratory study is to examine whether the addition of aripiprazole to naltrexone will enhance efficacy over naltrexone alone in a 16-week randomized, placebo-controlled clinical trial, in which all subjects will be provided medical management as delivered in the COMBINE Study (Anton et al, 2006). To test whether medication treatment will reduce drinking compared to placebo treatment alone in the context of medical management and whether naltrexone plus aripiprazole will reduce drinking compared to naltrexone treatment alone in the context of medical management.

Study Overview

• Status: Completed
• Conditions: Alcohol Dependence
• Intervention / Treatment: Drug: Placebo; Drug: Naltrexone; Drug: Naltrexone + Aripiprazole

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina, Center for Drug and Alcohol Programs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 70

2. Subjects will meet criteria for primary alcohol dependence operationalized as follows:

   A. Meets the DSM IV criteria for alcohol dependence including loss of control over drinking (criterion 3) B. Has not had more than one previous inpatient medical detoxification

3. Consumes, on average, at least 10 standard drinks per drinking day for men and 8 drinks per day for women in the 90 days pre-screening (to select an appropriately heavy drinking population)
4. Able to maintain sobriety for four days (with or without the aid of alcohol detoxification medications) as determined by self report, collateral 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 dependency disorder except nicotine dependence
2. Ever abused opiates
3. Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report, collateral report, or urine drug screen
4. Meets DSM IV criteria for current 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
5. Meets DSM IV current criteria for dissociative disorder or eating disorders
6. Has current suicidal ideation or homicidal ideation
7. Need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications
8. Current use of disulfiram
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 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 and a reliable source of collateral reporting
14. Has taken an opiate antagonist drug in the last month
15. Has taken aripiprazole in the last month or has experienced adverse effects from it at any time in the past

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1	Drug: Placebo; placebo
Active Comparator: 2; Naltrexone	Drug: Naltrexone; Naltrexone (25mg or 50 mg per titration schedule)
Active Comparator: 3; Naltrexone + Aripiprazole	Drug: Naltrexone + Aripiprazole; Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drinks Per Drinking Day	Standard drinks per drinking day	16-week treatment period
Percent Heavy Drinking Days	percent of total 112 day trial in which heavy drinking occurred (>=4 for females, >=5 male)	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pill Counts During Treatment	Compliance with medication as determined by pill counts	16-week
Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance	Riboflavin was added to each individual capsule of medication and measured as a proxy for compliance with the medication regime	16 weeks treatment trial

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Raymond F Anton, M.D., Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: April 24, 2008
• First Submitted That Met QC Criteria: April 24, 2008
• First Posted (Estimate): April 28, 2008

Study Record Updates

• Last Update Posted (Actual): September 29, 2017
• Last Update Submitted That Met QC Criteria: August 31, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Alcohol Dependence; Aripiprazole; Naltrexone; Alcoholism; Substance Abuse
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Narcotic Antagonists; Alcohol Deterrents; Aripiprazole; Naltrexone
• Other Study ID Numbers: ANTON-1R21AA017525-01; R21AA017525 (U.S. NIH Grant/Contract); NIH Grant AA017525-01