HIV Infections, Substance Abuse
Conditions
Keywords
Methamphetamine, HIV, MSM, HIV Seronegativity
Brief summary
Studies demonstrate that methamphetamine (meth) use is associated with high-risk sexual behavior among men who have sex with men (MSM), putting meth-using MSM at extraordinarily high risk for transmitting or acquiring HIV. This study is a randomized, double-blind, placebo-controlled trial of the medication aripiprazole for methamphetamine-using individuals, including MSM, and will assess efficacy, acceptability, tolerability, safety, and adherence to study medication.
Detailed description
Population-based surveys estimate that the prevalence of methamphetamine use is 20 times higher among men who have sex with men (MSM) compared to the general population. Methamphetamine-associated sexual risk behavior is also a driving force in the MSM HIV epidemic: methamphetamine use has been associated with increased number of sexual partners, unprotected sex acts, sexually transmitted infections (STIs), and HIV acquisition. Despite these alarming data, relatively few interventions have been tested among methamphetamine-using MSM. Among heterosexual non-injection drug users, methamphetamine use has been associated with well characterized risks for HIV and STDs including increased numbers of sexual partners, less condom use than non-methamphetamine users, engaging in sex work, and self-reported history of STDs. In parallel with the continued testing of behavioral approaches, we believe the time has come to test the feasibility and acceptability of pharmacologic interventions to reduce methamphetamine use among high-risk individuals. Pharmacologic approaches to treating substance use have been successful in treating nicotine, alcohol, and heroin dependencies. Preliminary dosing studies demonstrate that aripiprazole (Abilify), an FDA-approved, well-tolerated antipsychotic and partial dopamine agonist, reduced the effects of methamphetamine in humans and exhibited a good safety profile. We propose to expand upon these promising results by conducting a randomized, double-blind, placebo-controlled pilot study of aripiprazole among sexually-active, methamphetamine-dependent individuals. The specific aims of this study are: 1. To test the hypothesis that aripiprazole 20 mg daily will reduce methamphetamine use significantly more than placebo among methamphetamine-dependent individuals, as determined by the proportion of methamphetamine-negative urines and by self-report of methamphetamine use in the aripiprazole versus placebo group. 2. To measure the acceptability of aripiprazole and placebo among methamphetamine-dependent individuals, by determining (via electronic pill caps and self-report) medication adherence to aripiprazole and placebo. 3. To measure the safety and tolerability of aripiprazole and placebo among methamphetamine-dependent individuals, as determined by the number of adverse clinical events in the aripiprazole and placebo arms. If promising, study results will be used to design larger, definitive clinical trials to determine the efficacy of aripiprazole in reducing methamphetamine use and corresponding methamphetamine-associated sexual risk among MSM. This pilot study is therefore designed to reflect the structure of such trials. We will enroll 90 sexually active, methamphetamine-dependent individuals who will be randomized 1:1 to receive aripiprazole (n=45) or placebo (n=45) for 12 weeks. Because we are testing a drug for a new indication in a new population, we will include extensive safety parameters, as done in prior studies of pharmacologic interventions among substance users. We will also include both urine testing and extensive behavioral risk assessments because we anticipate that future definitive efficacy trials will analyze both substance use and sexual risk behavior outcomes. Study participants will be seen at the San Francisco Department of Public Health AIDS Office where they will provide urines for drug testing and participate in substance use counseling. All participants will receive HIV risk-reduction counseling. Behavior will be assessed using standardized measures via audio computer-assisted self-interview (ACASI).
Interventions
DRUGAripiprazole
DRUGPlacebo
Sugar pill manufactured to mimic Aripiprazole gel caps.
Sponsors
National Institute on Drug Abuse (NIDA)
San Francisco Department of Public Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
A total of 90 high-risk individuals with methamphetamine dependence will be enrolled in the study. Subjects will be San Francisco Bay Area residents between 18-60 years of age and in good health. The project is designed specifically for those at high risk for HIV transmission or acquisition. Inclusion Criteria: 1. HIV-negative by rapid test, or documentation of HIV infection with a laboratory result of a positive HIV test; 2. diagnosed with methamphetamine dependence as determined by SCID; 3. interested in stopping or reducing methamphetamine use; 4. at least one methamphetamine-positive urine during screening and run-in period; 5. no current acute illnesses requiring prolonged medical care; 6. no chronic illnesses that are likely to progress clinically during trial participation; 7. able and willing to provide informed consent and to be followed over trial period; 8. age 18-60 years; 9. baseline CBC, total protein, albumin, glucose, lipid panel, alk phos, creatinine, BUN, and electrolytes without clinically significant abnormalities as determined by investigator in conjunction with symptoms, physical exam, and medical history. 10. if sex assigned at birth was female and able to become pregnant: agrees to use birth control by any of the following methods - hormonal patch, pills, or injections; IUD; diaphragm; condoms; or abstinence.
Exclusion criteria
1. has a psychiatric disorder as assessed by SCID that in the opinion of evaluating clinician would make the study participation unsafe, or make adherence to study protocol untenable. Conditions include current major depression, current suicidal ideation, bipolar disorder, dementia, or acute psychosis; 2. taking psychotropic medication within the last 30 days, including aripiprazole; 3. known allergy to aripiprazole, or known adverse reaction to antipsychotics; 4. currently using or unwilling not to use phenylephrine or ephedrine-containing products for trial duration (can cause false positive urines for methamphetamine use); 5. current CD4 count \< 200 cells/mm3; 6. using other medications known to interact with aripiprazole, including ketoconazole and carbamazepine; 7. measured moderate or severe liver disease (AST, ALT, and total bilirubin \> 3 times normal) and/or any symptoms of current liver disease; 8. impaired renal function (creatinine clearance \< 60 ml/min); 9. diabetes mellitis type I or type II, including cases controlled with diet alone; 10. Hypertension that is not well-controlled; 11. BMI ≥ 40; or BMI ≥ 35 with more than one of the following: age \> 45, systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 90 mm Hg, known hyperlipidemia; 12. History of, or known active cardiovascular disease including: (a) Previous myocardial infarction (heart attack); (b) angina pectoris; (c) congestive heart failure; (d) valvular heart disease including mitral valve prolapse; (e) cardiomyopathy; (f) pericarditis; (g) stroke or transient ischemic attack; (h) chest pain or shortness of breath with activity (such as walking up stairs); (i) peripheral vascular disease or risk equivalent; (j) other heart conditions under the care of a doctor; 13. currently participating in another research study; 14. pregnant, breast-feeding, and/or positive pregnancy test at screening or enrollment visit; 15. any condition that, in the principal investigator's judgment, interferes with safe study participation or adherence to study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Test the Hypothesis That Aripiprazole 20 mg Daily Will Reduce Methamphetamine Use Significantly More Than Placebo Among Methamphetamine-dependent Individuals. | Final study visit at week 12 | To test the hypothesis that aripiprazole 20 mg daily will reduce methamphetamine use significantly more than placebo among methamphetamine-dependent individuals, as determined by the proportion of methamphetamine-positive urines in the aripiprazole versus placebo group. |
| To Measure the Acceptability of Aripiprazole and Placebo Among Methamphetamine-dependent Individuals, by Determining (Via Electronic Pill Caps [MEMS or Medication Event Monitoring System]) Medication Adherence to Aripiprazole and Placebo. | Adherence as determined by MEMS (throughout study, up to 12 weeks) | To measure the acceptability of aripiprazole and placebo among methamphetamine-dependent individuals, by determining (via electronic pill caps \[MEMS or Medication Event Monitoring System\]) medication adherence to aripiprazole and placebo. (Percent adherence from MEMS is determined by 100\* the number of days where MEMS registered an opening out of the number of days a dose was prescribed for each arm.) |
| To Measure the Safety and Tolerability of Aripiprazole and Placebo Among Methamphetamine-dependent Individuals, as Determined by the Number of Adverse Clinical Events in the Aripiprazole and Placebo Arms. | Total reported adverse events (throughout study, up to 12 weeks) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole aripiprazole daily for 3 months | 45 |
| Placebo placebo daily for 3 months | 45 |
| Total | 90 |
Baseline characteristics
| Characteristic | Placebo | Aripiprazole | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 45 Participants | 90 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 8.9 | 37.4 years STANDARD_DEVIATION 12.3 | 38.7 years STANDARD_DEVIATION 10.8 |
| Region of Enrollment United States | 45 participants | 45 participants | 90 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 40 Participants | 39 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 45 | 36 / 45 |
| serious Total, serious adverse events | 3 / 45 | 4 / 45 |
Outcome results
Primary
To Measure the Acceptability of Aripiprazole and Placebo Among Methamphetamine-dependent Individuals, by Determining (Via Electronic Pill Caps [MEMS or Medication Event Monitoring System]) Medication Adherence to Aripiprazole and Placebo.
To measure the acceptability of aripiprazole and placebo among methamphetamine-dependent individuals, by determining (via electronic pill caps \[MEMS or Medication Event Monitoring System\]) medication adherence to aripiprazole and placebo. (Percent adherence from MEMS is determined by 100\* the number of days where MEMS registered an opening out of the number of days a dose was prescribed for each arm.)
Time frame: Adherence as determined by MEMS (throughout study, up to 12 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole | To Measure the Acceptability of Aripiprazole and Placebo Among Methamphetamine-dependent Individuals, by Determining (Via Electronic Pill Caps [MEMS or Medication Event Monitoring System]) Medication Adherence to Aripiprazole and Placebo. | 46 percent adherence from MEMS | Standard Deviation 32 |
| Placebo | To Measure the Acceptability of Aripiprazole and Placebo Among Methamphetamine-dependent Individuals, by Determining (Via Electronic Pill Caps [MEMS or Medication Event Monitoring System]) Medication Adherence to Aripiprazole and Placebo. | 39 percent adherence from MEMS | Standard Deviation 27 |
p-value: 0.31Wilcoxon (Mann-Whitney)
Primary
To Measure the Safety and Tolerability of Aripiprazole and Placebo Among Methamphetamine-dependent Individuals, as Determined by the Number of Adverse Clinical Events in the Aripiprazole and Placebo Arms.
Time frame: Total reported adverse events (throughout study, up to 12 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aripiprazole | To Measure the Safety and Tolerability of Aripiprazole and Placebo Among Methamphetamine-dependent Individuals, as Determined by the Number of Adverse Clinical Events in the Aripiprazole and Placebo Arms. | 156 total reported adverse events |
| Placebo | To Measure the Safety and Tolerability of Aripiprazole and Placebo Among Methamphetamine-dependent Individuals, as Determined by the Number of Adverse Clinical Events in the Aripiprazole and Placebo Arms. | 144 total reported adverse events |
p-value: >=0.99Fisher Exact
Primary
To Test the Hypothesis That Aripiprazole 20 mg Daily Will Reduce Methamphetamine Use Significantly More Than Placebo Among Methamphetamine-dependent Individuals.
To test the hypothesis that aripiprazole 20 mg daily will reduce methamphetamine use significantly more than placebo among methamphetamine-dependent individuals, as determined by the proportion of methamphetamine-positive urines in the aripiprazole versus placebo group.
Time frame: Final study visit at week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aripiprazole | To Test the Hypothesis That Aripiprazole 20 mg Daily Will Reduce Methamphetamine Use Significantly More Than Placebo Among Methamphetamine-dependent Individuals. | 44 perc of positive urines at final visit |
| Placebo | To Test the Hypothesis That Aripiprazole 20 mg Daily Will Reduce Methamphetamine Use Significantly More Than Placebo Among Methamphetamine-dependent Individuals. | 40 perc of positive urines at final visit |
p-value: 0.4195% CI: [0.66, 1.16]Generalized estimating equation