Ondansetron, Alcohol Use, and Alcohol-Related Symptoms In HIV+ Persons

Study Overview
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Brief Summary
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The proposed randomized clinical trial will investigate a novel pharmacotherapy for hazardous drinking, HIV-infected men and women, using the serotonin receptor (5-HT3) antagonist ondansetron. The investigators predict that participants who are treated with active doses of ondansetron will reduce their drinking more and show better HIV treatment participation and progress compared to participants who are treated with placebo. This study will provide important new safety and efficacy results on drinking and HIV outcomes following alcohol pharmacotherapy in HIV-infected persons.

Detailed Description
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Hazardous drinking is particularly harmful in HIV-infected persons. It impairs the immune system, accelerates HIV disease progression, slows initiation of antiretroviral therapy (ART) and decreases adherence. Thus, the development of effective alcohol treatments for this clinical population is particularly important. The investigators are proposing to investigate the effectiveness of ondansetron pharmacotherapy for the treatment of hazardous alcohol use and alcohol abuse/dependence among HIV-infected patients. Ondansetron, a 5-HT3 antagonist, will be studied for several reasons: 1) evidence of effectiveness in persons who want to cut-down or reduce their drinking and who are not abstinent at medication initiation; 2) moderate-to-strong effects among early onset problem drinkers, a characteristic that is over represented in our clinic patients; 3) a very mild side-effect profile, making it an ideal pharmacotherapy candidate in patients who are often receiving multiple other medications with significant side-effects; and 4) its primary indication is for treatment of nausea, a common side-effect of antiretroviral (ARV) medications. The proposed study is a placebo-controlled, randomized clinical trial of ondansetron for the treatment of hazardous drinking and alcohol use disorders among HIV-infected patients recruited from the Baltimore/Washington area. Participants will be genotyped for a functional polymorphism of the serotonin transporter gene. They will be randomized to one of three treatment groups: placebo, low dose ondansetron (0.2 mg bid) and moderate dose ondansetron (0.8 mg bid). All subjects will undergo 16 weeks of pharmacotherapy in combination with medication management, and will be followed for 3 and 6 months after medication has ended.

Official Title
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Ondansetron Pharmacotherapy for Hazardous Drinking in HIV+, African-American Women

Conditions
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Alcohol Abuse, Alcohol Dependence

Intervention / Treatment
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* Drug: ondansetron
* Drug: placebo ondansetron
* Drug: Ondansetron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be at least 18 years old and HIV-infected All subjects will be actively drinking at hazardous levels (1) AUDIT score => 4 for women or =>8 for men, or 2) => 2 binge drinking episodes/month, or 3) >7 drinks/week for women or >14 drinks/week for men) Exclusion Criteria: Liver Function Tests (LFTs) > 5 X normal Magnesium or potassium > 3 X normal Qtc => .460 and or a family history of long QT syndrome (LQT) Inability to read and comprehend English Actively psychotic or other severe mental health symptoms that would prevent appropriate participation Current enrollment in alcoholism treatment program Pregnancy; Ondansetron is currently a category B drug. While animal data have not identified any harmful effects to mother or fetus, there have not been adequate human controlled trials to recommend routine use in this population

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Ondansetron - sugar pill<br>Placebo is an oral preparation made to appear and taste like the active drug preparation. | Drug: placebo ondansetron<br>* Matching placebo will be prepared using a colorless strawberry syrup, simple syrup and flat Schweppes tonic water.<br>|
| Experimental: low dose ondansetron (0.2 mg bid)<br> | Drug: ondansetron<br>* ondansetron 0.2 mg bid, oral preparation, 16 weeks<br>|
| Experimental: moderate dose ondansetron (0.8 mg bid)<br> | Drug: Ondansetron<br>* Ondansetron 0.8 mg bid, oral preparation, 16 weeks duration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Alcoholic Containing Drinks Per Drinking Day | The Time-line Follow-back (TLFB; Sobell, Sobell, Leo & Cancilla, 1988) is conducted as an interview administered by trained and certified research staff. The interview obtains participant self-reports of daily drinking, including number and type of alcoholic beverages. These data are used to quantify an individual's drinking pattern including the number of drinks per drinking day and drinking frequency. The TLFB was completed biweekly and quantified over the 16-week medication period | 16 weeks | 
| Number of Days/Week Abstinent From Alcohol | The Time-line Follow-back (Sobell, Sobell, Leo & Cancilla, 1988) is used to obtain this secondary dependent measure. Alcohol use will be assessed biweekly and quantified over the 16-week medication period. Number of days/week abstinent from alcohol is calculated as the number of abstinent days divided by the number of study medication days (adjusted for days in confinement (e.g., hospitalization; jail)) and multiplied by 7. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication Safety | Medication side-effects and adverse events were measured using the Systematic Assessment for Treatment of Emergent Events (SAFTEE). The SAFTEE contains 25 detailed questions that systematically address 29 body systems. A trained interviewer elicits information about onset, duration, pattern, and judgment of attribution. For the present trial outcome, we report number of events. | 16 weeks | 
| Number of Subjects Who Discontinue Due to Side Effects | The investigators will count the number of subjects who discontinue medication during the 16-week intervention period due to complaints of side effects. | 16 weeks | 
| Alcohol-related Problems | Alcohol-related problems were measured using the Short Inventory of Problems - revised (SIP-R), a self-report inventory of adverse consequences associated with alcohol and drug use. The SIP instructs participants to indicate how often each of 15 consequences has occurred during the past three months (never, once or a few times, once or twice a week, daily or almost daily; scored 0-3). Item responses are summed to produce a total score and five subscale scores. Total scores range from 0 - 45. | 16 weeks | 
| HIV Medication Adherence | The investigators will obtain patient self reports of the number of HIV medication doses taken as a function of the total number of doses prescribed. The adherence measure is expressed as the % of prescribed doses. | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV