Combined Pharmacotherapies for Alcoholism

Bankole Johnson

Status and phase: Completed; Phase 3

Conditions: Alcoholism

Treatments: Other: Placebo + Cognitive Behavioral Therapy; Drug: Naltrexone 50 mg/day + Cognitive Behavioral Therapy; Drug: Ondansetron 4 ug/kg b.i.d. + Cognitive Behavioral Therapy; Drug: Ondansetron 4 ug/kg b.i.d.+ Naltrexone 50 mg/day + Cognitive Behavioral Therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00768508

12790

R01AA012964 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 300 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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300 participants in 4 patient groups, including a placebo group

Ondansetron

Experimental group

Description:

Ondansetron 4 ug/kg b.i.d. + Cognitive Behavioral Therapy

Treatment:

Drug: Ondansetron 4 ug/kg b.i.d. + Cognitive Behavioral Therapy

Naltrexone

Experimental group

Description:

Naltrexone 50 mg/day + Cognitive Behavioral Therapy

Treatment:

Drug: Naltrexone 50 mg/day + Cognitive Behavioral Therapy

Ondansetron + Naltrexone

Experimental group

Description:

Ondansetron 4 ug/kg b.i.d. + Naltrexone 50 mg/day + Cognitive Behavioral Therapy

Treatment:

Drug: Ondansetron 4 ug/kg b.i.d.+ Naltrexone 50 mg/day + Cognitive Behavioral Therapy

Placebo

Placebo Comparator group

Description:

Placebo + Cognitive Behavioral Therapy

Treatment:

Other: Placebo + Cognitive Behavioral Therapy