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

NCT00780702 | Completed Phase 1

• 2 other identifiers: 99990842608-DA-N426
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cocaine Dependence; Cocaine-Related Disorders; Opioid-Related Disorders

Keywords

Cocaine; Treatment; Airpiprazole; Methadone; Relapse; HIV; Ecological Momentary Assessment (EMA); Contingency Management

Outcome Measures

Primary Outcomes (1)

• Time to relapse

  19 weeks

Secondary Outcomes (2)

• Cocaine use

  19 weeks

• HIV risk behaviors

  19 weeks

Study Arms (2)

Arm 1

EXPERIMENTAL

Drug: Airipiprazole

Arm 2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Airipiprazole DRUG

Participants receive aripiprazole (orally, up to 15 mg/day) plus standard methadone maintenance (daily oral methadone and weekly individual counseling).

Arm 1

Placebo DRUG

Participants receive identical capsules containing no active medication plus standard methadone maintenance (daily oral methadone and weekly individual counseling).

Arm 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 and 60
• Evidence of physical dependence on opioids (determined by self-report, urine screen, and physical exam)
• Evidence of (a) current cocaine use (determined by self-report and urine screen) or (b) cocaine dependence (DIS interview for DSM-IV criteria).
• Lifetime drug-use duration of at least 1 year and current cocaine use on at least 3 days of the last 30.
• Seeking treatment for opiate and cocaine use.
• Able to attend methadone clinic 7 days/week.

You may not qualify if:

• 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
• Allergy, hypersensitivity, or intolerance to either methadone or aripiprazole (determined by Self-Reported Medical History)
• AIDS, CD4 \<200, or evidence of severely compromised immune system (determined by Blood Laboratory tests; see details under Screening measures below)
• Pregnancy or breastfeeding (Urine Pregnancy Test; self report)
• 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.
• 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.
• ECG abnormalities including QTc interval \> 450 ms or changes suggesting acute ischemia, \<TAB\>second or third degree heart block, left bundle branch block, atrial fibrillation, or other \<TAB\>clinically important arrhythmias. ECGs may be sent to an outside cardiologist for manual \<TAB\>reading.
• Contraindicated medications (Self-Reported Medical History):

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse

Baltimore, Maryland, 21224, United States

Location

Related Publications (3)

• Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L, Kumar G, McLeod J, Obach SR, Roberts S, Roe A, Shah A, Snikeris F, Sullivan JT, Tweedie D, Vega JM, Walsh J, Wrighton SA; Pharmaceutical Research and Manufacturers of America Drug Metabolism/Clinical Pharmacology Technical Working Groups. The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J Clin Pharmacol. 2003 May;43(5):443-69.

  PMID: 12751267 BACKGROUND

• Childress AR, O'Brien CP. Dopamine receptor partial agonists could address the duality of cocaine craving. Trends Pharmacol Sci. 2000 Jan;21(1):6-9. doi: 10.1016/s0165-6147(99)01422-4. No abstract available.

  PMID: 10637646 BACKGROUND

• Conley RR, Kelly DL, Gale EA. Olanzapine response in treatment-refractory schizophrenic patients with a history of substance abuse. Schizophr Res. 1998 Sep 7;33(1-2):95-101. doi: 10.1016/s0920-9964(98)00062-0.

  PMID: 9783349 BACKGROUND

MeSH Terms

Conditions

Cocaine-Related Disorders; Opioid-Related Disorders; Recurrence

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Narcotic-Related Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kenzie Preston, Ph.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 27, 2008
• First Posted: October 28, 2008
• Study Start: May 8, 2008
• Primary Completion: April 16, 2013
• Study Completion: April 16, 2013
• Last Updated: December 16, 2019

Record last verified: 2014-02-27

Locations

US (1)