A New Pharmacotherapy for Alcohol Dependence: Olanzapine

NCT00746785 | Completed Phase 3 Results

• 1 other identifier: 5R01AA014886
• Study Type: interventional
• Target: 304
• Locations: 1 country
• Sites: 1

Brief Summary

Craving for alcohol has been related to loss of control drinking and is a major target of biological and behavioral interventions for alcohol dependence. Our previous research has demonstrated that olanzapine (a dopamine antagonist) attenuates craving for alcohol, that a variant in the gene that expresses D4 receptors influences craving for alcohol, and that olanzapine is particularly effective at reducing craving among individuals with this variant. Pilot data from a recent 12 week trial of olanzapine indicates that olanzapine is well tolerated and that olanzapine reduces drinking, particularly among individuals with the aforementioned genetic variant. The objective of the present application is to examine the effectiveness of olanzapine (5 mg/day), as compared to olanzapine (2.5 mg/day) and a placebo control, in terms of reducing craving and alcohol use behavior among treatment seeking alcoholics. Furthermore, the present application will examine whether the effects of olanzapine on drinking outcomes are mediated by its effects on a specific putative mechanism (i.e., cue-elicited craving for alcohol) and determine whether the DRD4 VNTR polymorphism is a marker for the effectiveness of olanzapine. To that end, 202 alcohol dependent subjects will be randomly assigned to medication group and receive 12 weeks of medication. Subjects will complete follow-up assessments at 3 and 6 months after the end of the treatment. It is expected that olanzapine will significantly reduce cue-elicited craving and alcohol use behavior in a dose dependent fashion over the course of the 12 week trial and follow-up period, as compared to the placebo condition. Furthermore, it is expected that the effects of olanzapine on alcohol use behavior will be mediated by the effect of olanzapine on cue-elicited craving and that the effects of olanzapine on cue-elicited craving and alcohol use behavior will be moderated by the DRD4 VNTR, such that olanzapine will be more effective among individuals with the 7 repeat allele. The successful completion of the proposed research is expected to advance a new medication for alcohol dependence and advance genetic markers that predict the effectiveness of this medication.

Conditions

Alcohol Dependence

Keywords

Olanzapine

Outcome Measures

Primary Outcomes (1)

• Drinks Per Drinking Day

  Drinks are measured as the number of standard alcoholic beverages consumed each day, assessed in varying lengths of time (i.e., 2 weeks, 4 weeks, 6 weeks, etc.). A standard alcoholic beverage is equivalent to: 1, 12 oz. regular beer; 1, 5 oz. glass of wine; 1, mixed drink with one1.5 oz shot; or 1, 1.5 oz shot. A drinking day is measured as any day of the week in which an alcoholic beverage is consumed. Data for drinks per drinking day is gathered using the "Time Line Follow Back" method in which participants are asked to recall their alcohol consumption day by day for a pre-defined set of time.

  up to 36 weeks

Study Arms (3)

2.5 mg Olanzapine

EXPERIMENTAL

2.5 mg Olanzapine 1x per day for 12 weeks.

Drug: 2.5 mg Olanzapine

5mg Olanzapine

ACTIVE COMPARATOR

5 mg Olanzapine 1x per day for 12 weeks.

Drug: 5mg Olanzapine

Placebo

PLACEBO COMPARATOR

Placebo 1x per day for 12 weeks.

Drug: placebo

Interventions

2.5 mg Olanzapine DRUG

2.5 mg

2.5 mg Olanzapine

5mg Olanzapine DRUG

5 mg

5mg Olanzapine

placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years of age with
• Alcohol Dependence

You may not qualify if:

• Medical Contraindications

Sponsors & Collaborators

• The Mind Research Network: lead

Study Sites (1)

The Mind Research Network

Albuquerque, New Mexico, 87131, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Kent Hutchison, Ph.D.
• Organization: The Mind Reseach Network

khutchison@mrn.org

505-272-5028

Study Officials

• Kent E Hutchison, Ph.D.

  The Mind Research Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Science Officer

Study Record Dates

• First Submitted: September 2, 2008
• First Posted: September 4, 2008
• Study Start: September 1, 2002
• Primary Completion: May 1, 2010
• Study Completion: September 1, 2011
• Last Updated: March 20, 2014
• Results First Posted: March 20, 2014

Record last verified: 2014-01

Locations

US (1)