Clinical trial NCT01254877: Ondansetron, Alcohol Use, and Alcohol-Related Symptoms In HIV+ Persons
Official title: Ondansetron Pharmacotherapy for Hazardous Drinking in HIV+, African-American Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcohol Abuse
Alcohol Dependence
Keywords: HIV
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2010-12-07
Enrollment: 357
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Alcoholic Containing Drinks Per Drinking Day
timeFrame: 16 weeks
measure: Number of Days/Week Abstinent From Alcohol
timeFrame: 16 weeks
Secondary outcomes:
measure: Medication Safety
timeFrame: 16 weeks
measure: Number of Subjects Who Discontinue Due to Side Effects
timeFrame: 16 weeks
measure: Alcohol-related Problems
timeFrame: 16 weeks
measure: HIV Medication Adherence
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Mary E McCaul, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Johnson BA, Roache JD, Javors MA, DiClemente CC, Cloninger CR, Prihoda TJ, Bordnick PS, Ait-Daoud N, Hensler J. Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: A randomized controlled trial. JAMA. 2000 Aug 23-30;284(8):963-71. doi: 10.1001/jama.284.8.963.