Aripiprazole for Prevention of Relapse to Cocaine Use in Methadone-Maintenance Patients

• Status: Completed
• Trial end date: 2013-04-16
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• The effectiveness of methadone maintenance for treatment of heroin addiction has been well established. However, patients maintained on methadone may relapse to cocaine use, even when they are enrolled in a comprehensive treatment program. Relapse has been attributed to several factors, including drug-associated environmental stimuli.

• Aripiprazole is a drug used to treat schizophrenia and bipolar disorder, but it may have other uses. Research has shown that aripiprazole can reduce cocaine-seeking behavior in rats, and it has been investigated for use in treating amphetamine dependence. More research is needed to determine whether aripiprazole can prevent relapse to cocaine use in patients being treated with methadone.

Objectives:

• To determine whether aripiprazole prevents relapse to cocaine use more effectively than placebo in cocaine-abstinent patients maintained on methadone.

Eligibility:

• Individuals between 18 and 60 years of age who are current cocaine users seeking methadone treatment.

Design:

• The study will last up to 41 weeks, with four phases of treatment and a follow-up evaluation. Three times a week, participants will be asked to report illicit drug use and provide urine and breath samples. Throughout the study, participants will receive individual counseling in weekly 40 60 minute sessions. Other samples and tests will be scheduled as required by the study researchers.

• Patients will be stabilized on daily methadone over the first 14 days of the study.

• Weeks 1 14: Participants will receive vouchers for regular cocaine-free urine samples. Those who successfully complete this phase will continue to the next part of the study.

• Weeks 13 27: Participants will receive either aripiprazole or placebo along with their methadone. During this part of the study, participants will keep electronic diaries to record cocaine use or craving and to record data on mood and activity.

• Weeks 28 33: Participants will stop taking the aripiprazole or placebo, but will continue the methadone treatment. Participants will continue to use the electronic diaries.

• Weeks 34 41: Participants will have the choice of transferring to a community clinic or gradually reducing doses of methadone to end the study.

• Participants will return for a follow-up visit and urine sample 6 months after the end of the study.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute on Drug Abuse (NIDA)
• Treatments: Aripiprazole; Cocaine; Methadone

Criteria

• INCLUSION CRITERIA:

1. Age between 18 and 60

2. Evidence of physical dependence on opioids (determined by self-report, urine screen, and physical exam)

3. Evidence of (a) current cocaine use (determined by self-report and urine screen) or (b) cocaine dependence (DIS interview for DSM-IV criteria).

4. Lifetime drug-use duration of at least 1 year and current cocaine use on at least 3 days of the last 30.

5. Seeking treatment for opiate and cocaine use.

6. Able to attend methadone clinic 7 days/week.

EXCLUSION CRITERIA:

1. Any medical illness that in the view of the investigators would compromise participation in research (determined by Self-Reported Medical History; Physical Examination; Blood and Urine Laboratory tests; see details under Screening measures below), including, but not limited to:

• cardiovascular disease

• cerebrovascular disease

• unexplained history of syncope

• history of seizures, except for febrile seizures at childhood

• chronic renal failure, as estimated by Cr > 2.0

• diabetes mellitus

• hyperlipidemia

2. Allergy, hypersensitivity, or intolerance to either methadone or aripiprazole (determined by Self-Reported Medical History)

3. AIDS, CD4 <200, or evidence of severely compromised immune system (determined by Blood Laboratory tests; see details under Screening measures below)

4. Pregnancy or breastfeeding (Urine Pregnancy Test; self report)

5. Orthostatic hypotension (i.e., upon standing for 3 minutes, a 20 mm Hg decrease in systolic blood pressure or a 10 mmHg decrease in diastolic blood pressure, accompanied by an increase by 20 bpm in heart rate) on two separate readings during physical examination.

6. Marked, sustained high blood pressure (SBP >160 mm Hg, DBP >100 mm Hg) on two or more readings at a single visit and confirmed with two readings on a follow-up visit. If a participant is started on antihypertensive drugs at the start of the study, the participant may be cleared, but will not be started on aripiprazole until confirmation that the hypertension is well controlled (systolic blood pressure < 150, diastolic blood pressure < 100 mm Hg) on two readings at least 3 days apart.

7. ECG abnormalities including QTc interval > 450 ms or changes suggesting acute ischemia,second or third degree heart block, left bundle branch block, atrial fibrillation, or other clinically important arrhythmias. ECGs may be sent to an outside cardiologist for manual reading.

8. Contraindicated medications (Self-Reported Medical History):

• Alpha-1 receptor blockers (e.g., doxazin, terazosin)

• Anti-epileptic medications (e.g., carbamazepine)

• Tricyclic antidepressants

• SSRIs

• Neuroleptics

• Quinidine

• Antifungals (e.g., ketoconazole)

• Ranolazine

• CYP3A4 inhibitors or inducers (other than methadone)

• CYP2D6 inhibitors or inducers (other than methadone)

9. Family history (Self-Reported Medical History):

• Family history of sudden death of unexplained causes

• Sudden cardiac death

• Aneurysm

• Myocardial infarction below the age 50 years

10. Psychiatric history:

A) Cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires (Shipley Institute of Living scale estimated full-scale IQ less than 80)

B) History of schizophrenia or any other DSM-IV psychotic disorder (Self-Reported Medical History; Diagnostic Interview Schedule for the DSM-IV (DIS IV))

C) History of bipolar disorder (Self-Reported Medical History; DIS IV)

D) Current Major Depressive Disorder (Self-Reported Medical History; DIS IV)

E) Previous suicide attempts or ideation (Self-Reported Medical History; DIS-IV)

F) Dementia (DIS-IV; Clinical Interview; Shipley Institute of Living scale)

11. Current physical dependence on alcohol or sedative-hypnotics, e.g. benzodiazepines (self-report; ASI; alcohol CAGE questions; and pattern of positive drug screens or BAL for alcohol)

12. Body Mass Index (BMI) over 40

13. Failure to agree to use a medically effective form of contraception while in the study (in women who are sexually active with a male partner and able to get pregnant). Acceptable forms of contraception for this study include:

• hormonal contraceptives (birth control pills, injectable hormones, vaginal ring hormones),

• surgical sterility (tubal ligation or hysterectomy)

• IUD

• Diaphragm with spermicide

• Condom with spermicide