Effects of Aripiprazole on Cocaine Craving and Self-Administration

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00373880
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 26
• Location: 1
• Arms: 2
• Duration (Months): 41
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Cocaine Abuse	Drug: Aripiprazole + Cocaine; Drug: Placebo + Cocaine	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• 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.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.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effects of Aripiprazole on Cocaine Craving and Self-Administration
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole (15mg) + Cocaine Aripiprazole (15 mg/day) in conjunction with a smoked cocaine dose-response curve (0, 12, 25, 50 mg).	Drug: Aripiprazole + Cocaine; Participants received aripiprazole (15mg/day) in conjunction with a dose-response of cocaine (0, 12, 25, 50 mg).; Other Names: Active
Placebo Comparator: Placebo + Cocaine Placebo (0 mg/day) in conjunction with a smoked cocaine dose-response curve (0, 12, 25, 50 mg)	Drug: Placebo + Cocaine; Placebo (0 mg/day) in conjunction with a dose-response of cocaine (0, 12, 25, 50 mg).; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Cocaine Self-administration [5 days]

   Mean number of cocaine choices as a function of cocaine dose and aripiprazole dose (n=8). Participants sampled the dose of cocaine available for the session and then had five choices to respond for money ($5.00) or cocaine using a modified progressive-ratio schedule.

Secondary Outcome Measures

1. Subjective Effects of Cocaine [5 days]

   Mean Visual Analog Scale (VAS) ratings (items: "Quality", "Pay for Dose", "Good Drug Effect", and "Cocaine Craving") from 0-100mm as a function of cocaine dose and aripiprazole dose 4 min following a single administration of cocaine (the "sample dose") at the start of the session. For "Quality" item, the perceived quality of the drug is rated. The higher the rating, the better quality the drug was perceived to be. For "Pay for Dose" item, the likelihood that the participant would pay for the drug is indicated. Higher ratings indicate a better likelihood that the person would pay for the dose received. For "Good Drug Effect", the likelihood of feeling a good drug effect is indicated. The higher the number, the more of a good drug effect the person reported. For "Cocaine Craving", the intensity of craving is reported. Higher scores indicate more craving for cocaine.

2. Plasma Cocaine [8 minutes]

   Mean plasma cocaine levels after a single administration of each cocaine dose as a function of aripiprazole and cocaine dose.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Irving Center for Clinical Research	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Margaret Haney, Ph.D., New York State Psychiatric Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT00373880
• Other Study ID Numbers: 4741
• First Posted: Sep 8, 2006
• Last Update Posted: Sep 11, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by New York State Psychiatric Institute: Aripiprazole; Cocaine abuse
• Additional relevant MeSH terms: Cocaine-Related Disorders; Cocaine; Aripiprazole

Study Results

Participant Flow

Arm/Group Title	Aripiprazole/Placebo, Cocaine
Arm/Group Description	aripiprazole (15 mg/day) or placebo (0mg/day) + smoked cocaine dose-response curve (0, 12, 25, 50 mg)
Period Title: Overall Study
STARTED	26
COMPLETED	8
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	Aripiprazole vs. Placebo
Arm/Group Description	Aripiprazole + Cocaine: Participants received aripiprazole (15mg/day) or placebo (o mg/day) in conjunction with a dose-response of cocaine (0, 12, 25, 50 mg).
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.8 (3.9)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	8 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 62.5%
White	3 37.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Cocaine Self-administration
Description	Mean number of cocaine choices as a function of cocaine dose and aripiprazole dose (n=8). Participants sampled the dose of cocaine available for the session and then had five choices to respond for money ($5.00) or cocaine using a modified progressive-ratio schedule.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Eight participants were included in this within-subjects analysis.

Arm/Group Title	Placebo + 0mg Cocaine	Placebo + 12mg Cocaine	Placebo + 25mg Cocaine	Placebo + 50mg Cocaine	Aripiprazole + 0 mg Cocaine	Aripiprazole + 12mg Cocaine	Aripiprazole + 25mg Cocaine	Aripiprazole + 50mg Cocaine
Arm/Group Description	Participants received placebo (0 mg/day) in conjunction with 0 mg cocaine.	Participants received placebo (0 mg/day) in conjunction with 12 mg cocaine.	Participants received placebo (0 mg/day) in conjunction with 25 mg cocaine.	Participants received placebo (0 mg/day) in conjunction with 50 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 0 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 12 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 25 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 50 mg cocaine.
Measure Participants	8	8	8	8	8	8	8	8
Mean (Standard Error) [Number of Choices]	0 (0)	1.5 (0.5)	3 (0.5)	4 (0.5)	0.2 (0.1)	2.8 (0.5)	3.9 (0.5)	3.7 (0.5)

2. Secondary Outcome

Title	Subjective Effects of Cocaine
Description	Mean Visual Analog Scale (VAS) ratings (items: "Quality", "Pay for Dose", "Good Drug Effect", and "Cocaine Craving") from 0-100mm as a function of cocaine dose and aripiprazole dose 4 min following a single administration of cocaine (the "sample dose") at the start of the session. For "Quality" item, the perceived quality of the drug is rated. The higher the rating, the better quality the drug was perceived to be. For "Pay for Dose" item, the likelihood that the participant would pay for the drug is indicated. Higher ratings indicate a better likelihood that the person would pay for the dose received. For "Good Drug Effect", the likelihood of feeling a good drug effect is indicated. The higher the number, the more of a good drug effect the person reported. For "Cocaine Craving", the intensity of craving is reported. Higher scores indicate more craving for cocaine.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Eight participants were included in this within-subjects analysis.

Arm/Group Title	Placebo + 0mg Cocaine	Placebo + 12mg Cocaine	Placebo + 25mg Cocaine	Placebo + 50mg Cocaine	Aripiprazole + 0 mg Cocaine	Aripiprazole + 12mg Cocaine	Aripiprazole + 25mg Cocaine	Aripiprazole + 50mg Cocaine
Arm/Group Description	Participants received placebo (0 mg/day) in conjunction with 0 mg cocaine.	Participants received placebo (0 mg/day) in conjunction with 12 mg cocaine.	Participants received placebo (0 mg/day) in conjunction with 25 mg cocaine.	Participants received placebo (0 mg/day) in conjunction with 50 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 0 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 12 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 25 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 50 mg cocaine.
Measure Participants	8	8	8	8	8	8	8	8
Quality	0 (0)	8.5 (0.5)	32 (5)	38.5 (6)	0 (0)	10 (0.4)	25 (5)	37 (6)
Pay for Dose	0 (0)	1.4 (0.5)	5 (1)	5.75 (1)	0 (0)	1.6 (0.2)	2.9 (0.3)	6 (1.5)
Good Drug Effect	1 (0.1)	11 (2)	29 (5)	42 (5)	2 (0.1)	16 (3)	30.5 (5)	35 (6)
Cocaine Craving	20 (5)	28 (5)	30 (5)	38.5 (5)	26 (6)	30 (5)	36 (6)	33.5 (6)

3. Secondary Outcome

Title	Plasma Cocaine
Description	Mean plasma cocaine levels after a single administration of each cocaine dose as a function of aripiprazole and cocaine dose.
Time Frame	8 minutes

Outcome Measure Data

Analysis Population Description

Eight participants were included in this within-subjects analysis.

Arm/Group Title	Placebo + 0mg Cocaine	Placebo + 12mg Cocaine	Placebo + 25mg Cocaine	Placebo + 50mg Cocaine	Aripiprazole + 0 mg Cocaine	Aripiprazole + 12mg Cocaine	Aripiprazole + 25mg Cocaine	Aripiprazole + 50mg Cocaine
Arm/Group Description	Participants received placebo (0 mg/day) in conjunction with 0 mg cocaine.	Participants received placebo (0 mg/day) in conjunction with 12 mg cocaine.	Participants received placebo (0 mg/day) in conjunction with 25 mg cocaine.	Participants received placebo (0 mg/day) in conjunction with 50 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 0 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 12 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 25 mg cocaine.	Participants received aripiprazole (15 mg/day) in conjunction with 50 mg cocaine.
Measure Participants	8	8	8	8	8	8	8	8
Mean (Standard Deviation) [ng/mL]	32 (2)	60 (4)	67 (4)	119 (12)	18 (1)	36 (3)	75 (5)	130 (10)

Adverse Events

Time Frame	2 years
Arm/Group Title	Aripiprazole vs. Placebo		Placebo
Arm/Group Description	Aripiprazole + Cocaine: Participants received aripiprazole (15mg/day) in conjunction with a dose-response of cocaine (0, 12, 25, 50 mg).		Placebo + Cocaine: Participants received placebo (0 mg/day) in conjunction with a dose-response of cocaine (0, 12, 25, 50 mg).
All Cause Mortality
	Aripiprazole vs. Placebo		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Aripiprazole vs. Placebo		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Aripiprazole vs. Placebo		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)

Limitations/Caveats

The study did not assess whether the medication would be useful in preventing relapse in abstinent cocaine users or whether aripiprazole would be beneficial to cocaine-dependent individuals being treated for a psychiatric comorbidity.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.