Alcohol Abuse, Alcohol Dependence
Conditions
Keywords
HIV
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.
Interventions
DRUGondansetron
ondansetron 0.2 mg bid, oral preparation, 16 weeks
DRUGplacebo ondansetron
Matching placebo will be prepared using a colorless strawberry syrup, simple syrup and flat Schweppes tonic water.
DRUGOndansetron
Ondansetron 0.8 mg bid, oral preparation, 16 weeks duration
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Alcoholic Containing Drinks Per Drinking Day | 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 |
| Number of Days/Week Abstinent From Alcohol | 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
| Measure | Time frame | Description |
|---|---|---|
| Medication Safety | 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. |
| Number of Subjects Who Discontinue Due to Side Effects | 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. |
| Alcohol-related Problems | 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. |
| HIV Medication Adherence | 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. |
Countries
United States
Participant flow
Pre-assignment details
357 persons signed informed consent; 205 were randomized. 137 exclusions were mainly due to insufficient alcohol use (as determined by self-report or biomarker), abnormal QT interval, or significant mental health symptoms that precluded assessment completion. An additional 13 participants withdrew, were discontinued by the investigators or died.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Ondansetron - Sugar Pill Placebo is an oral preparation made to appear and taste like the active drug preparation.
placebo ondansetron: Matching placebo will be prepared using a colorless strawberry syrup, simple syrup and flat Schweppes tonic water. | 67 |
| Low Dose Ondansetron (0.2 mg Bid) ondansetron: ondansetron 0.2 mg bid, oral preparation, 16 weeks | 69 |
| Moderate Dose Ondansetron (0.8 mg Bid) Ondansetron: Ondansetron 0.8 mg bid, oral preparation, 16 weeks duration | 69 |
| Total | 205 |
Baseline characteristics
| Characteristic | Placebo Ondansetron - Sugar Pill | Low Dose Ondansetron (0.2 mg Bid) | Moderate Dose Ondansetron (0.8 mg Bid) | Total |
|---|---|---|---|---|
| Age, Continuous | 49.7 years STANDARD_DEVIATION 8.7 | 48.7 years STANDARD_DEVIATION 8.2 | 47.8 years STANDARD_DEVIATION 9.5 | 48.7 years STANDARD_DEVIATION 8.8 |
| Number of days abstinent from alcohol/week | 2.9 days/week STANDARD_DEVIATION 1.9 | 3.0 days/week STANDARD_DEVIATION 2.1 | 3.3 days/week STANDARD_DEVIATION 1.9 | 3.1 days/week STANDARD_DEVIATION 2 |
| Number of drinks per drinking day | 9.1 standard alcohol drink STANDARD_DEVIATION 5.5 | 10.5 standard alcohol drink STANDARD_DEVIATION 7.7 | 10.0 standard alcohol drink STANDARD_DEVIATION 8.7 | 9.9 standard alcohol drink STANDARD_DEVIATION 7.3 |
| Race/Ethnicity, Customized Black | 65 Participants | 66 Participants | 64 Participants | 195 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 67 Participants | 69 Participants | 69 Participants | 205 Participants |
| Sex: Female, Male Female | 21 Participants | 23 Participants | 27 Participants | 71 Participants |
| Sex: Female, Male Male | 46 Participants | 46 Participants | 42 Participants | 134 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 67 | 0 / 67 | 1 / 69 |
| other Total, other adverse events | 7 / 67 | 5 / 69 | 8 / 69 |
| serious Total, serious adverse events | 16 / 67 | 20 / 69 | 5 / 69 |
Outcome results
Primary
Number of Alcoholic Containing Drinks Per Drinking Day
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
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Ondansetron - Sugar Pill | Number of Alcoholic Containing Drinks Per Drinking Day | 5.9 Standard alcohol drinks per drinking day | Standard Deviation 3.8 |
| Low Dose Ondansetron (0.2 mg Bid) | Number of Alcoholic Containing Drinks Per Drinking Day | 6.1 Standard alcohol drinks per drinking day | Standard Deviation 4.3 |
| Moderate Dose Ondansetron (0.8 mg Bid) | Number of Alcoholic Containing Drinks Per Drinking Day | 5.9 Standard alcohol drinks per drinking day | Standard Deviation 3.9 |
Primary
Number of Days/Week Abstinent From Alcohol
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.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Ondansetron - Sugar Pill | Number of Days/Week Abstinent From Alcohol | 4.7 days/week abstinent from alcohol | Standard Deviation 2.2 |
| Low Dose Ondansetron (0.2 mg Bid) | Number of Days/Week Abstinent From Alcohol | 4.9 days/week abstinent from alcohol | Standard Deviation 2 |
| Moderate Dose Ondansetron (0.8 mg Bid) | Number of Days/Week Abstinent From Alcohol | 4.8 days/week abstinent from alcohol | Standard Deviation 2.2 |
Secondary
Alcohol-related Problems
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.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Ondansetron - Sugar Pill | Alcohol-related Problems | 6.6 units on a scale | Standard Deviation 7.3 |
| Low Dose Ondansetron (0.2 mg Bid) | Alcohol-related Problems | 7.5 units on a scale | Standard Deviation 7.9 |
| Moderate Dose Ondansetron (0.8 mg Bid) | Alcohol-related Problems | 8.3 units on a scale | Standard Deviation 15.7 |
Secondary
HIV Medication Adherence
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.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Ondansetron - Sugar Pill | HIV Medication Adherence | 92.4 percentage of prescribed doses | Standard Deviation 31.6 |
| Low Dose Ondansetron (0.2 mg Bid) | HIV Medication Adherence | 87.6 percentage of prescribed doses | Standard Deviation 37.6 |
| Moderate Dose Ondansetron (0.8 mg Bid) | HIV Medication Adherence | 85.4 percentage of prescribed doses | Standard Deviation 31.7 |
Secondary
Medication Safety
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.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Ondansetron - Sugar Pill | Medication Safety | 11.4 number of events | Standard Deviation 11.1 |
| Low Dose Ondansetron (0.2 mg Bid) | Medication Safety | 12.4 number of events | Standard Deviation 13.4 |
| Moderate Dose Ondansetron (0.8 mg Bid) | Medication Safety | 11.0 number of events | Standard Deviation 12.3 |
Secondary
Number of Subjects Who Discontinue Due to Side Effects
The investigators will count the number of subjects who discontinue medication during the 16-week intervention period due to complaints of side effects.
Time frame: 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Ondansetron - Sugar Pill | Number of Subjects Who Discontinue Due to Side Effects | 0 Participants |
| Low Dose Ondansetron (0.2 mg Bid) | Number of Subjects Who Discontinue Due to Side Effects | 0 Participants |
| Moderate Dose Ondansetron (0.8 mg Bid) | Number of Subjects Who Discontinue Due to Side Effects | 0 Participants |