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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01254877
Recruitment Status : Completed
First Posted : December 7, 2010
Last Update Posted : March 9, 2017
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Mary E. McCaul, Johns Hopkins University

Brief Summary:
The proposed randomized clinical trial will investigate a novel pharmacotherapy for hazardous drinking, HIV-infected men and women, using the 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.

Condition or disease Intervention/treatment Phase
Alcohol Abuse Alcohol Dependence Drug: ondansetron Drug: placebo ondansetron Drug: Ondansetron Phase 2

Detailed Description:

Hazardous drinking is particularly harmful in HIV-infected persons. It impairs the immune system, accelerates HIV disease progression, slows initiation of 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 357 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Ondansetron Pharmacotherapy for Hazardous Drinking in HIV+, African-American Women
Study Start Date : December 2010
Primary Completion Date : January 2017
Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

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

Primary Outcome Measures :
  1. number of drinks per drinking day [ Time Frame: 16 weeks ]
    The Time-line Follow-back (Sobell, Sobell, Leo & Cancilla, 1988) is used to obtain the primary dependent measure. Alcohol use is assessed biweekly and quantified over the 16-week medication period

  2. Total number of days abstinent from alcohol [ Time Frame: 16 weeks ]
    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. Total number of days abstinent will be calculated as the number of abstinent days divided by the number of days elapsed (adjusted for days in confinement (e.g., hospitalization; jail)).

Secondary Outcome Measures :
  1. medication safety [ Time Frame: 16 weeks ]
    Medication side-effects and adverse events will be measured using the SAFTEE.

  2. Number of subjects who discontinue due to side effects [ Time Frame: 16 weeks ]
    The investigators will count the number of subjects who discontinue medication during the 16-week intervention period due to complaints of side effects.

  3. Alcohol-related problems [ Time Frame: 16 weeks ]
    The investigators will measure alcohol-related problems using the SIP-2R, a widely used and well validated instrument.

  4. HIV medication persistence [ Time Frame: 16 weeks ]
    The investigators will obtain patient self reports of HIV medication persistence as well as a visual analog scale of % persistence.

  5. HIV risk behaviors [ Time Frame: 16 weeks ]
    Risk behaviors will be measured based on self report

  6. Quality of life [ Time Frame: 16 weeks ]
    Quality of life will be measured based on subject self report.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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:

  • LFTs > 5 X normal
  • Magnesium or potassium > 3 X normal
  • Qtc => .460 and or a family history of 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01254877

United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Johns Hopkins University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Principal Investigator: Mary E McCaul, Ph.D. Johns Hopkins University

Responsible Party: Mary E. McCaul, Professor, Johns Hopkins University Identifier: NCT01254877     History of Changes
Other Study ID Numbers: R01AA018896 ( U.S. NIH Grant/Contract )
First Posted: December 7, 2010    Key Record Dates
Last Update Posted: March 9, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Mary E. McCaul, Johns Hopkins University:

Additional relevant MeSH terms:
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents