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

Johns Hopkins University

Status and phase: Completed; Phase 2

Conditions: Alcohol Abuse; Alcohol Dependence

Treatments: Drug: placebo ondansetron; Drug: ondansetron; Drug: Ondansetron

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01254877

NA_00032774

R01AA018896 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 357 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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357 participants in 3 patient groups, including a placebo group

Placebo Ondansetron - sugar pill

Placebo Comparator group

Description:

Placebo is an oral preparation made to appear and taste like the active drug preparation.

Treatment:

Drug: placebo ondansetron

low dose ondansetron (0.2 mg bid)

Experimental group

Treatment:

Drug: ondansetron

moderate dose ondansetron (0.8 mg bid)

Experimental group

Treatment:

Drug: Ondansetron