Combined Pharmacotherapies for Alcoholism

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Combined Pharmacotherapies for Alcoholism

Conditions
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Alcoholism

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcohol, Alcohol Dependence, Alcoholism