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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Johns Hopkins University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mary E. McCaul, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01254877
First received: December 6, 2010
Last updated: August 28, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Alcohol Abuse
Alcohol Dependence
Drug: ondansetron
Drug: placebo ondansetron
Drug: Ondansetron
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Ondansetron Pharmacotherapy for Hazardous Drinking in HIV+, African-American Women

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • number of drinks per drinking day [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    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

  • Total number of days abstinent from alcohol [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    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:
  • medication safety [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    Medication side-effects and adverse events will be measured using the SAFTEE.

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

  • Alcohol-related problems [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    The investigators will measure alcohol-related problems using the SIP-2R, a widely used and well validated instrument.

  • HIV medication persistence [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    The investigators will obtain patient self reports of HIV medication persistence as well as a visual analog scale of % persistence.

  • HIV risk behaviors [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Risk behaviors will be measured based on self report

  • Quality of life [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Quality of life will be measured based on subject self report.


Estimated Enrollment: 300
Study Start Date: December 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo - 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

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 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01254877

Contacts
Contact: Mary E McCaul, Ph.D. (410)502-2723 mmccaul1@jhmi.edu
Contact: Geetanjali Chander, M.D. (443) 287-2030 gchande1@jhmi.edu

Locations
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21205
Principal Investigator: Mary E McCaul, Ph.D.         
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Mary E McCaul, Ph.D. Johns Hopkins University
  More Information

Publications:
Responsible Party: Mary E. McCaul, Professor, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01254877     History of Changes
Other Study ID Numbers: R01AA018896, R01AA018896
Study First Received: December 6, 2010
Last Updated: August 28, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
HIV

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Ondansetron
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipruritics
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

ClinicalTrials.gov processed this record on July 20, 2014