Psychopharmacology for Cocaine Dependence - Buspirone

NCT01267292 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NIDA-P50-09262-Project2.1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cocaine Dependence

Keywords

cocaine dependence; psychopharmacology; attentional bias; risky decision making; buspirone; methylphenidate

Outcome Measures

Primary Outcomes (2)

• Attentional Bias as Assessed by Score on the Stroop Task

  The mean score over all 4 time points is reported in this outcome measure (i.e., a summary score is reported). Each subject contributed 1 data point for each dose level of Methylphenidate (15mg, 30mg, 60mg, or 0mg), resulting in a total of 20 data points per dose level per arm. The Stroop task assesses attentional biases to cocaine-related (drug-related) and rewarding (non-drug related) stimuli vs. neutral stimuli. Participants are instructed to respond to words shown in different colors on the screen, by pressing as quickly and accurately as possible on one of three colored buttons. Attentional bias is measured as the difference in reaction times on cocaine vs. neutral words. The reported score is a difference score in milliseconds (cocaine minus neutral), in which positive means slower to respond to cocaine and thus greater attentional bias, and negative means no attentional bias to cocaine words.

  1 time a day on Wednesday and Friday of week 2; 1 time a day on Monday and Wednesday of week 3

• Risky Decision Making as Assessed by Score on the Risky Decision Making Task

  The mean score over all 4 time points is reported in this outcome measure (i.e., a summary score is reported). Each subject contributed 1 data point for each dose level of Methylphenidate (15mg, 30mg, 60mg, or 0mg), resulting in a total of 20 data points per dose level per arm. The risky decision making task provides subjects with three choice options on each of 100 repeated trials. Options are low, moderate, and high risk, based on variance and probability in gain/loss amounts. The low risk option is more adaptive over many trials. The outcome measure is a risk index (ranging from 0.33 to 100) that factors in tolerance for variability and amount of gains and losses across the three options. 100 is highest risk. 0.33 is lowest risk.

  1 time a day on Wednesday and Friday of week 2; 1 time a day on Monday and Wednesday of week 3

Secondary Outcomes (13)

• Subjective Effects as Assessed by the Addiction Research Center Inventory (ARCI)

  11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3

• Subjective Effects as Assessed by Score on the Vigor Subscale of the Profile of Mood States (POMS)

  11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3

• Subjective Effects as Assessed by Score on the "Feel High" Subscale of the Drug Effects Questionnaire (DEQ)

  11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3

• Subjective Effects as Assessed by the "Elated" Subscale of the Visual Analogue Scale (VAS)

  11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3

• Heart Rate

  11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3

Study Arms (2)

Buspirone plus Methylphenidate

EXPERIMENTAL

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

Drug: Buspirone; Drug: Methylphenidate; Drug: Placebo for Methylphenidate

Placebo for Buspirone plus Methylphenidate

PLACEBO COMPARATOR

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

Drug: Placebo for Buspirone; Drug: Methylphenidate; Drug: Placebo for Methylphenidate

Interventions

Buspirone DRUG

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

Also known as: Buspar

Buspirone plus Methylphenidate

Placebo for Buspirone DRUG

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

Also known as: corn starch

Placebo for Buspirone plus Methylphenidate

Methylphenidate DRUG

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

Also known as: Ritalin

Buspirone plus Methylphenidate; Placebo for Buspirone plus Methylphenidate

Placebo for Methylphenidate DRUG

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

Also known as: corn starch

Buspirone plus Methylphenidate; Placebo for Buspirone plus Methylphenidate

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Buspirone; Starch; Methylphenidate

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Polysaccharides; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Piperidines

Results Point of Contact

• Title: Scott Lane, PhD
• Organization: The University of Texas Health Science Center at Houston

Scott.D.Lane@uth.tmc.edu

713-486-2535

Study Officials

• Scott D Lane, Ph.D.

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor - Psychiatry & Behavioral Sciences

Study Record Dates

• First Submitted: December 24, 2010
• First Posted: December 28, 2010
• Study Start: March 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 4, 2017
• Results First Posted: May 4, 2017

Record last verified: 2017-05

Locations

US (1)