Official Title: “Ondansetron With Olanzapine for the Treatment of Alcohol Dependence: A Preliminary Clinical Trial”

This study would like to test whether the combination of ondansetron and olanzapine will be superior to placebo at decreasing self-reported heavy drinking among early onset alcoholics.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2008

Target population: We will enroll male and female who meet DSM IV criteria for alcohol dependence and who are currently drinking equal or more than 21 alcohol units/week for women and equal or more than 28 alcohol units/week for men in the 7 day period prior to enrollment.

This is a double-blind placebo-controlled study. Eligible subjects will be randomized to ondansetron (4 ug/kg) and olanzapine (9, 18, 36 ug/kg) vs placebo. All subjects will participate in a 9 week regimen of weekly BBCET and outpatient medication treatment.

Intervention(s) in this Clinical Trial

• Drug: Ondansetron
  • ondansetron (4 μg/kg b.i.d.)
• Drug: Olanzapine
  • olanzapine (9, 18, and 36 μg/kg)
• Drug: Placebo
  • placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: ondansetron/olanzapine
  • ondansetron (4 μg/kg b.i.d.) olanzapine (9 μg/kg)
• Placebo Comparator: placebo
  • placebo

Primary Measures

• The combination of ondansetron and olanzapine will be safe and superior to placebo at decreasing self-reported heavy drinking among early-onset alcoholics.
  • Time Frame: Throughout the study
    Safety Issue?: No

Secondary Measures

• The combination of ondansetron and olanzapine will be superior to placebo at reducing the psychosocial consequences of drinking.
  • Time Frame: Throughout the study
    Safety Issue?: No

Inclusion Criteria:

• Males and females who have given written informed consent
• Aged 18 years and above and weighing ≥40 kg and ≤140 kg
• Drinking on average ≥21 and ≥28 drinks/week for women and men, respectively, in the 7-day period prior to enrollment
• DSM-IV-R diagnosis of alcohol dependence
• Good physical health as determined by a complete physical examination, electrocardiogram (EKG) within normal limits and laboratory screening tests within acceptable range
• Negative pregnancy test at intake.
• Literate in English and able to read, understand, and complete the rating scales and questionnaires accurately, follow instructions, and make use of the behavioral treatments
• Willing to participate in behavioral treatments for alcoholism
• Answer an advertisement in the newspaper/radio/television, and express a wish to stop drinking
• Provide evidence of stable residence in the last month prior to enrollment in the study, and have no plans to move in the next three months

Exclusion Criteria:

• Any current axis I DSM-IV psychiatric disorder other than alcohol or nicotine dependence that warrants treatment or would preclude safe participation in the protocol
• Severe alcohol withdrawal symptoms that, in the physician's opinion, require inpatient treatment
• Serious medical comorbidity requiring medical intervention or close supervision, or any condition that can interfere with the receipt of ondansetron or olanzapine
• Severe or life-threatening adverse reactions to the ondansetron or olanzapine medications in the past or during this clinical trial
• Female subjects who are pregnant, lactating, or not adhering to an acceptable form of contraception at any time during the study
• Received inpatient or outpatient treatment for alcohol dependence within the last 30 days
• Significant medical illness (including hypertension) as determined by history and/or complete physical examination.
• Gross neurological disease
• Mental retardation
• Pyrexia of unknown origin
• Diagnosis or suspicion of Alzheimer's disease
• Clinically significant abnormalities on the EKG that will preclude safe participation
• Recent (last 3 months) history of ischemic heart disease or myocardial infarction.
• Current infective hepatitis as evidenced by clinical manifestations. If hepatitis is suspected, a hepatitis antibody/antigen screen will be done.
• Participation in a clinical study within the last 30 days
• Elevation of liver enzymes
• History of any severe or life-threatening reaction to olanzapine or ondansetron
• Past or current history of seizures disorder
• Past or current history of diabetes
• Being treated with any medication with potential for clinically significant interactions with alcohol or olanzapine and/or ondansetron. These include:, serotonin antagonists (e.g., ritanserin or buspirone), dopamine antagonists (e.g., haloperidol), or compounds with actions similar to disulfiram (Antabuse®).
• Pending imprisonment

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Virginia

Overall Clinical Trial Officials and Contacts

Bankole Johnson, DSc, MD, PhD Principal Investigator University of Virginia  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00678457

Study ID Number: TO45228

ClinicalTrials.gov Identifier: NCT00678457

Health Authority: United States: Food and Drug Administration