Psychopharmacology for Cocaine Dependence - Buspirone

NCT ID: NCT01267292

Last Updated: 2017-05-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-31

Study Completion Date

2015-12-31

Brief Summary

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Chronic cocaine use may produce disruption of neurotransmitter functions (including dopamine). This may in turn contribute to measurable dysfunction in important cognitive and behavioral processes. Stimulants that enhance dopamine (DA) function may help in treating cocaine dependence and improving behavioral function -- supporting the notion that these processes are related. An important step is to understand the subjective, physiological, and behavioral effects of potential medications for cocaine dependence.

DA-modulating drugs may be targets for pharmacotherapy for substance dependence, and particularly for stimulant drugs like cocaine, which disrupt normal DA function. Buspirone is currently the only available dopamine subtype 3 (DA3) approved for human administration, and is thus a viable investigational compound.

This project proposes to evaluate the DA-modulating effects of buspirone on behavioral deficiencies related to DA depletion. Accordingly, the project aims to characterize the effects of buspirone in individuals with cocaine dependence. Employing a daily dosing designs within an acute stimulant challenge (methylphenidate), the experiment will characterize the subjective effects, cardiovascular effects, and behavioral effects (attentional bias to drug cues and risky decision making). The primary hypotheses are that buspirone will attenuate the increases in subjective drug effects ("stimulated", "like drug") and behavioral effects (increases in attentional bias and risky decision making) that are produced by acute methylphenidate administration.

Detailed Description

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Chronic cocaine use may produce disruption of monoamine systems (including dopamine). This may in turn contribute to measurable dysfunction in important cognitive and behavioral processes. Pharmacotherapy with stimulants that enhance dopamine (DA) function has shown efficacy in treating cocaine dependence and improving behavioral function -- supporting the notion that these processes are related. In the development of novel pharmacotherapies for cocaine dependence, an important step is a full characterization of the psychopharmacological properties of potential medications for cocaine dependence, including subjective, physiological, and behavioral effects. Selective medications may play a key role in the modulation of DA neurotransmission by enhancing DA receptor activation.

The D3 receptor is an autoreceptor that may function to control phasic DA activity and mediate sensitization of DA agonists, thus playing a role in conditioning of drugs of abuse like cocaine. Growing evidence suggests that D3 receptor antagonists may be targets for pharmacotherapy for substance dependence, and particularly for stimulant drugs like cocaine, which disrupt normal DA function. Importantly, administration of D3 antagonists may disrupt reactivity (attention) to drug cues and attenuate cue-induced craving. Buspirone is currently the only available D3 antagonist approved for human administration, and is thus a viable investigational compound.

This project proposes to evaluate the potential pharmacotherapeutic action of the D3 antagonist buspirone. The DA-modulating effects of buspirone may help with affective and behavioral deficiencies related to DA depletion. Accordingly, the project aims to characterize the psychopharmacology of buspirone in individuals with cocaine dependence. Employing chronic dosing designs within an acute stimulant challenge (methylphenidate), the experiment will be conducted using well-established psychopharmacological methods in order to characterize the shape and magnitude of chronic pretreatment-mediated change in the methylphenidate dose-response curve. Measures will include subjective effects, cardiovascular effects, and behavioral effects (attentional bias to drug cues and risky decision making). These data will compliment and provide valuable information to clinical trials using these agents to treat cocaine dependence.

Conditions

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Cocaine Dependence

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Buspirone plus Methylphenidate

\[week 1: Buspirone 30 mg twice a day (9am and 6pm) on Monday through Sunday; no Methylphenidate or Methylphenidate placebo\] \[week 2: Buspirone 45 mg twice a day (9am and 6pm) on Monday through Sunday; 0mg Methylphenidate (placebo) on Monday at 10am; Methylphenidate once a day (10am) on Wednesday and Friday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\] \[week 3: Buspirone 45 mg twice a day (9am and 6pm) on Monday through Sunday; Methylphenidate once a day (10am) on Monday and Wednesday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\]

Group Type EXPERIMENTAL

Buspirone

Intervention Type DRUG

\[week 1: Buspirone 30 mg twice a day (9am and 6pm) on Monday through Sunday\] \[weeks 2-3: Buspirone 45 mg twice a day (9am and 6pm) on Monday through Sunday\]

Methylphenidate

Intervention Type DRUG

Methylphenidate serves as an acute stimulant challenge. \[week 1: no Methylphenidate or Methylphenidate placebo\] \[week 2: 0mg Methylphenidate (placebo for Methylphenidate) on Monday at 10am; Methylphenidate once a day (10am) on Wednesday and Friday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\] \[week 3: Methylphenidate once a day (10am) on Monday and Wednesday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\]

Placebo for Methylphenidate

Intervention Type DRUG

\[week 1: no Methylphenidate or Methylphenidate placebo\] \[week 2: 0mg Methylphenidate (placebo for Methylphenidate) on Monday at 10am; Methylphenidate once a day (10am) on Wednesday and Friday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\] \[week 3: Methylphenidate once a day (10am) on Monday and Wednesday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\]

Placebo for Buspirone plus Methylphenidate

\[week 1: Placebo for Buspirone twice a day (9am and 6pm) on Monday through Sunday; no Methylphenidate or Methylphenidate placebo\] \[week 2: Placebo for Buspirone twice a day (9am and 6pm) on Monday through Sunday; 0mg Methylphenidate (placebo for Methylphenidate) on Monday at 10am; Methylphenidate once a day (10am) on Wednesday and Friday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\] \[week 3: Placebo for Buspirone twice a day (9am and 6pm) on Monday through Sunday; Methylphenidate once a day (10am) on Monday and Wednesday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\]

Group Type PLACEBO_COMPARATOR

Placebo for Buspirone

Intervention Type DRUG

\[week 1: Placebo for Buspirone twice a day (9am and 6pm) on Monday through Sunday\] \[weeks 2-3: Placebo for Buspirone twice a day (9am and 6pm) on Monday through Sunday\]

Methylphenidate

Intervention Type DRUG

Methylphenidate serves as an acute stimulant challenge. \[week 1: no Methylphenidate or Methylphenidate placebo\] \[week 2: 0mg Methylphenidate (placebo for Methylphenidate) on Monday at 10am; Methylphenidate once a day (10am) on Wednesday and Friday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\] \[week 3: Methylphenidate once a day (10am) on Monday and Wednesday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\]

Placebo for Methylphenidate

Intervention Type DRUG

\[week 1: no Methylphenidate or Methylphenidate placebo\] \[week 2: 0mg Methylphenidate (placebo for Methylphenidate) on Monday at 10am; Methylphenidate once a day (10am) on Wednesday and Friday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\] \[week 3: Methylphenidate once a day (10am) on Monday and Wednesday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\]

Interventions

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Buspirone

\[week 1: Buspirone 30 mg twice a day (9am and 6pm) on Monday through Sunday\] \[weeks 2-3: Buspirone 45 mg twice a day (9am and 6pm) on Monday through Sunday\]

Intervention Type DRUG

Placebo for Buspirone

\[week 1: Placebo for Buspirone twice a day (9am and 6pm) on Monday through Sunday\] \[weeks 2-3: Placebo for Buspirone twice a day (9am and 6pm) on Monday through Sunday\]

Intervention Type DRUG

Methylphenidate

Methylphenidate serves as an acute stimulant challenge. \[week 1: no Methylphenidate or Methylphenidate placebo\] \[week 2: 0mg Methylphenidate (placebo for Methylphenidate) on Monday at 10am; Methylphenidate once a day (10am) on Wednesday and Friday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\] \[week 3: Methylphenidate once a day (10am) on Monday and Wednesday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\]

Intervention Type DRUG

Placebo for Methylphenidate

\[week 1: no Methylphenidate or Methylphenidate placebo\] \[week 2: 0mg Methylphenidate (placebo for Methylphenidate) on Monday at 10am; Methylphenidate once a day (10am) on Wednesday and Friday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\] \[week 3: Methylphenidate once a day (10am) on Monday and Wednesday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)\]

Intervention Type DRUG

Other Intervention Names

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Buspar corn starch Ritalin corn starch

Eligibility Criteria

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Inclusion Criteria

* cocaine dependent subjects, non-treatment seeking
* meet current DSM-IV criteria for cocaine dependence disorder
* report using cocaine within the past 30 days
* at least 1 positive urine toxicology screen for the cocaine metabolite benzoylecgonine (BE) \[300 ng/mL, during the initial (2-4 day) screening period
* acceptable health on the basis of interview, medical history, and physical exam
* able to understand the consent form and provide written informed consent.

Exclusion Criteria

* currently dependent on any psychoactive substance other than cocaine or nicotine
* current DSM-IV diagnosed major psychiatric disorder (e.g., psychosis, bipolar, major depressive disorder)
* any medical condition that would contraindicate administration of medications
* taking medications known to have significant drug interactions study medications
* probation / parole requiring reports of drug use to court officers
* pregnant or nursing for female patients
* cannot read, write, or speak English.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The University of Texas Health Science Center, Houston

OTHER

Sponsor Role lead

Responsible Party

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Scott Lane

Professor - Psychiatry & Behavioral Sciences

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Scott D Lane, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

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The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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NIDA-P50-09262-Project2.1

Identifier Type: -

Identifier Source: org_study_id

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