Combined Pharmacotherapies for Alcoholism

This study would like to test whether the combination of ondansetron and naltrexone will be superior to either medication alone or placebo in the treatment of alcohol dependence.

Study Overview

• Status: Completed
• Conditions: Alcoholism
• Intervention / Treatment: Drug: Ondansetron 4 ug/kg b.i.d. + Cognitive Behavioral Therapy; Drug: Naltrexone 50 mg/day + Cognitive Behavioral Therapy; Drug: Ondansetron 4 ug/kg b.i.d.+ Naltrexone 50 mg/day + Cognitive Behavioral Therapy; Other: Placebo + Cognitive Behavioral Therapy

Detailed Description

We propose to conduct a 13 week randomized, controlled clinical trial to evaluate the safety and efficacy of ondansetron and naltrexone alone and in combination.Eligible subjects will be randomized to placebo, ondansetron, naltrexone, or ondansetron + naltrexone treatments. All subjects will receive a weekly CBT (Cognitive Behavioral Therapy)sessions.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • UVA CARE
    • Richmond, Virginia, United States, 23294
      • UVA CARE Richmond

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males and females who have given written informed consent.
• Ages 18 years and above and must weigh at least 40 kg and no more than 140 kg.
• Good physical health as determined by a complete physical examination, an EKG within normal limits, and laboratory screening tests within acceptable parameters (see exclusion criteria).
• Current DSM-IV diagnosis of alcohol dependence
• AUDIT score of equal or more than 8.
• Currently 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.
• The pregnancy test for females at intake must be negative. Additionally, women of childbearing potential must be using an acceptable form of contraception. These include: oral contraceptives, hormonal (levonorgestrel) or surgical implants, or barrier plus spermicide.
• Literate in English and able to read, understand, and complete the ratings scales and questionnaires accurately, follow instructions, and make use of the behavioral treatments.
• Answer an advertisement in the newspaper/radio/television, or be referred from a health care professional and express a wish to stop drinking.
• Willingness to participate in behavioral treatments for alcoholism.

Exclusion Criteria:

• Any current axis I DSM IV psychiatric disorder other than alcohol or nicotine dependence
• Elevation of liver enzymes - (SGOT), serum glutamic pyruvic transaminase (SGPT), blood urea nitrogen (BUN), or lactate dehydrogenase (LDH) greater than four times the normal range, or clinically significant elevated direct bilirubin as deemed by the principal investigator.
• Severe alcohol withdrawal symptoms which in the physicians opinion requires inpatient treatment.
• Serious medical co-morbidity requiring medical intervention or close supervision, or any condition which can interfere with the receipt of ondansetron.
• Severe or life-threatening adverse reactions to medications in the past or during this clinical trial.
• Female patients 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 (support groups such as AA are not exclusionary).
• Compelled to participate in an alcohol treatment program to maintain their liberty.
• Members of the same household.
• Concurrent treatment with any medications having a potential effect on alcohol consumption and related behaviors, or mood. These include: opiate antagonist (e.g. naltrexone), glutamate antagonists (e.g., acamprosate), serotonin re-uptake inhibitors (e.g. fluoxetine), serotonin antagonists (e.g. ritanserin or buspirone), other antidepressants (e.g. tricylic antidepressants or monoamine oxidase inhibitors), dopamine antagonists (e.g. haloperidol), calcium channel antagonists (e.g. isradipine), or compounds with actions similar to disulfiram (antabuse) or nicotine.
• Before double-blind randomization, urine must be free of opiates, cocaine, amphetamines, barbiturates, benzodiazepines, prescription and non-prescription drugs.
• Pyrexia of unknown origin

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ondansetron; Ondansetron 4 ug/kg b.i.d. + Cognitive Behavioral Therapy	Drug: Ondansetron 4 ug/kg b.i.d. + Cognitive Behavioral Therapy; Ondansetron 4 ug/kg b.i.d.for 12 weeks; Other Names: Zofran
Experimental: Naltrexone; Naltrexone 50 mg/day + Cognitive Behavioral Therapy	Drug: Naltrexone 50 mg/day + Cognitive Behavioral Therapy; Naltrexone 50 mg/day for 12 weeks; Other Names: Revia
Experimental: Ondansetron + Naltrexone; Ondansetron 4 ug/kg b.i.d. + Naltrexone 50 mg/day + Cognitive Behavioral Therapy	Drug: Ondansetron 4 ug/kg b.i.d.+ Naltrexone 50 mg/day + Cognitive Behavioral Therapy; Combination of ondansetron 4 ug/kg b.i.d. and naltrexone 50 mg/day for 12 weeks; Other Names: Zofran and Revia
Placebo Comparator: Placebo; Placebo + Cognitive Behavioral Therapy	Other: Placebo + Cognitive Behavioral Therapy; Placebo comparator; Other Names: sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-report measures of alcohol-related problems and consumption, Objective measures of alcohol consumption	Drinks per drinking day, Drinks per day, Percent Days Abstinent, BAC, CDT, GGT	Throughout the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication compliance, alcohol craving, social functioning, quality of life, alcohol withdrawal, attendance at psychosocial services, pre-morbid risk factors	Pill Count, SFQ, AASE, ADBS, OCDS, CIWA-Ar, CGI, TCI, MAC, AOQ, FHAM	Throughout the study

Collaborators and Investigators

• Sponsor: Bankole Johnson
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Bankole Johnson, DSc,MD,PhD, University of Virginia

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: October 6, 2008
• First Submitted That Met QC Criteria: October 6, 2008
• First Posted (Estimate): October 8, 2008

Study Record Updates

• Last Update Posted (Estimate): March 15, 2013
• Last Update Submitted That Met QC Criteria: March 14, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Alcohol Dependence; Alcohol; Alcoholism
• 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; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Narcotic Antagonists; Alcohol Deterrents; Antipruritics; Naltrexone; Ondansetron
• Other Study ID Numbers: 12790; R01AA012964 (U.S. NIH Grant/Contract)