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| ID | Type | Description | Link |
|---|---|---|---|
| R01AA018896 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo Ondansetron - sugar pill | Placebo Comparator | Placebo is an oral preparation made to appear and taste like the active drug preparation. |
|
| low dose ondansetron (0.2 mg bid) | Experimental |
| |
| moderate dose ondansetron (0.8 mg bid) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ondansetron | Drug | ondansetron 0.2 mg bid, oral preparation, 16 weeks |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 16 weeks |
| 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. | 16 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mary E McCaul, Ph.D. | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Hospital | Baltimore | Maryland | 21205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10944641 | Background | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Low Dose Ondansetron (0.2 mg Bid) | ondansetron: ondansetron 0.2 mg bid, oral preparation, 16 weeks |
| FG002 | Moderate Dose Ondansetron (0.8 mg Bid) | Ondansetron: Ondansetron 0.8 mg bid, oral preparation, 16 weeks duration |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Low Dose Ondansetron (0.2 mg Bid) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Mean | Standard Deviation | Standard alcohol drinks per drinking day | 16 weeks |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Alcohol Intoxication | Psychiatric disorders | Systematic Assessment | Acute alcohol intoxication treated in the Emergency Dept or inpatient hospitalization |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough/cold symptoms | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
Drinking data are based on patient self-report.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mary E McCaul | JohnHopkinsU | 410-955-9526 | mmccaul1@jhmi.edu |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D017294 | Ondansetron |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| placebo ondansetron |
| Drug |
Matching placebo will be prepared using a colorless strawberry syrup, simple syrup and flat Schweppes tonic water. |
|
| Ondansetron | Drug | Ondansetron 0.8 mg bid, oral preparation, 16 weeks duration |
|
| 16 weeks |
| 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. | 16 weeks |
| 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. | 16 weeks |
| 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. | 16 weeks |
ondansetron: ondansetron 0.2 mg bid, oral preparation, 16 weeks |
| BG002 | Moderate Dose Ondansetron (0.8 mg Bid) | Ondansetron: Ondansetron 0.8 mg bid, oral preparation, 16 weeks duration |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Number of drinks per drinking day | Mean | Standard Deviation | standard alcohol drink |
|
| Number of days abstinent from alcohol/week | Mean | Standard Deviation | days/week |
|
| OG001 | Low Dose Ondansetron (0.2 mg Bid) | ondansetron: ondansetron 0.2 mg bid, oral preparation, 16 weeks |
| OG002 | Moderate Dose Ondansetron (0.8 mg Bid) | Ondansetron: Ondansetron 0.8 mg bid, oral preparation, 16 weeks duration |
|
|
| 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. | Posted | Mean | Standard Deviation | days/week abstinent from alcohol | 16 weeks |
|
|
|
| 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. | Posted | Mean | Standard Deviation | number of events | 16 weeks |
|
|
|
| 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. | Posted | Count of Participants | Participants | 16 weeks |
|
|
|
| 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. | Posted | Mean | Standard Deviation | units on a scale | 16 weeks |
|
|
|
| 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. | Posted | Mean | Standard Deviation | percentage of prescribed doses | 16 weeks |
|
|
|
| 1 |
| 67 |
| 16 |
| 67 |
| 7 |
| 67 |
| EG001 | Low Dose Ondansetron (0.2 mg Bid) | ondansetron: ondansetron 0.2 mg bid, oral preparation, 16 weeks | 0 | 67 | 20 | 69 | 5 | 69 |
| EG002 | Moderate Dose Ondansetron (0.8 mg Bid) | Ondansetron: Ondansetron 0.8 mg bid, oral preparation, 16 weeks duration | 1 | 69 | 5 | 69 | 8 | 69 |
|
| Pneumonia/Respiratory Infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Psychiatric disorder | Psychiatric disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| cardiovascular event | Cardiac disorders | Systematic Assessment |
|
| Other | General disorders | Systematic Assessment |
|
| Alcohol intoxication/withdrawal | Psychiatric disorders | Systematic Assessment |
|
| Rash/wound infection | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Other | General disorders | Systematic Assessment |
|
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| D002227 |
| Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006575 | Heterocyclic Compounds, 3-Ring |