Aripiprazole Treatment for Methamphetamine Dependence Among High-risk Individuals
Information source: San Francisco Department of Public Health
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Substance Abuse; HIV Infections
Intervention: Aripiprazole (Drug); Placebo (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: San Francisco Department of Public Health Official(s) and/or principal investigator(s): Phillip O Coffin, MD, MIA, Principal Investigator, Affiliation: Director of Substance Use Research, San Francisco Department of Public Health
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.
Clinical Details
Official title: Aripiprazole Treatment for Methamphetamine Dependence Among High-risk Individuals
Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: To Test the Hypothesis That Aripiprazole 20 mg Daily Will Reduce Methamphetamine Use Significantly More Than Placebo Among Methamphetamine-dependent Individuals.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 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.
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).
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
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.
Locations and Contacts
San Francisco Department of Public Health, AIDS Office, San Francisco, California 94102, United States
Additional Information
Starting date: March 2009
Last updated: February 5, 2014
|