Clinical trial NCT00373880: Effects of Aripiprazole on Cocaine Craving and Self-Administration
Official title: Effects of Aripiprazole on Cocaine Craving and Self-Administration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cocaine Abuse
Keywords: Aripiprazole
Cocaine abuse
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2006-09-08
Enrollment: 26
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: In order to achieve steady-state concentrations, participants (n=8 men) were administered placebo and aripiprazole (15 mg/day) capsules in counter-balanced order for 21 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was determined twice under placebo and aripiprazole maintenance.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate whether aripiprazole will decrease cocaine self-administration, subjective effects and cravings compared to placebo.

Detailed description: Despite the recent increase in data about cocaine's basic neurochemical mechanisms of action, progress towards the development of an effective pharmacological treatment for cocaine abuse has been disappointing. We are proposing to use our laboratory model of repeated dose cocaine self-administration to assess the potential efficacy of the novel antipsychotic, aripiprazole. Aripiprazole is a partial agonist at both the dopamine D2 receptor and at the serotonin 5HT1a receptor, while antagonizing the 5HT2a receptor. By functioning as a partial D2 agonist, aripiprazole is hypothesized to function as a D2 antagonist during hypodopaminergic states, such as during cocaine use, while functioning as a D2 agonist during hypodopaminergic states, such as during cocaine withdrawal. This 42-day, outpatient/inpatient/outpatient/inpatient protocol will evaluate the effects of aripiprazole maintenance (0, 15 mg/day) on cocaine craving, subjective effects, and self-administration using a within-subjects design. Non-treatment seeking cocaine abusers will be maintained outpatient for 16 days of dose maintenance prior to inpatient cocaine self-administration sessions. During the inpatient phases, volunteers will live on a hospital clinical research unit and will participate in laboratory sessions in which they will have the opportunity to choose between repeated doses of smoked cocaine and $5. In addition to measuring their cocaine self-administration, we will measure the cardiovascular and subjective effects of cocaine under each aripiprazole maintenance condition.

Eligibility criteria: Inclusion Criteria:

* Meets DSM-IV criteria for current cocaine abuse
* Average use of smoked cocaine is at least 2x/week for past 6 mos); currently spends at least $70 per week on cocaine
* Has patterns of smoked cocaine use in terms of frequency and amounts which parallel or exceed those administered in the study
* Age 21-45
* Able to give informed consent, and comply with study procedures

Exclusion Criteria:

* Current seizure disorder, heart disease or psychiatric disorders (other than cocaine dependence)
* Dependence on substances other than cocaine or nicotine
* Request for drug treatment
* Judged to be noncompliant with study protocol
* Current use of any medication that has the potential to interact with aripiprazole (i.e., seizure medications, anti-fungal medications, cardiac medications, or medication that produces drowsiness)
* Clinical laboratory tests outside normal limits that are clinically unacceptable to the study physician (BP \> 140/90; BUN, creatinine, LFTs \> 1.5 ULN; hematocrit \< 34 for women, \< 36 for men; pseudocholinesterase deficiency)
* Currently meeting DSM-IV criteria for all major psychiatric/psychotic disorders other than transient psychosis due to drug abuse
* Current parole or probation
* History of significant violent or suicidal behavior

Primary outcomes:
measure: Cocaine Self-administration
timeFrame: 5 days
Secondary outcomes:
measure: Subjective Effects of Cocaine
timeFrame: 5 days
measure: Plasma Cocaine
timeFrame: 8 minutes
Other outcomes:
Locations:
city: New York
country: United States
facility: Irving Center for Clinical Research
state: New York
Study officials:
affiliation: New York State Psychiatric Institute
name: Margaret Haney, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: