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
Results First Posted : April 17, 2018
Last Update Posted : April 17, 2018
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
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 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.

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 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.

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
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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 Alcoholic Containing Drinks Per Drinking Day [ Time Frame: 16 weeks ]
    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

  2. Number of Days/Week 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. 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.

Secondary Outcome Measures :
  1. Medication Safety [ Time Frame: 16 weeks ]
    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.

  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 ]
    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.

  4. HIV Medication Adherence [ Time Frame: 16 weeks ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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:

  • 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

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: Johns Hopkins University Identifier: NCT01254877     History of Changes
Other Study ID Numbers: NA_00032774
R01AA018896 ( U.S. NIH Grant/Contract )
First Posted: December 7, 2010    Key Record Dates
Results First Posted: April 17, 2018
Last Update Posted: April 17, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by 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