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Psychopharmacology for Cocaine Dependence - Buspirone

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by The University of Texas Health Science Center, Houston
Sponsor:
Information provided by (Responsible Party):
Scott Lane, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT01267292
First received: December 24, 2010
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Cocaine Dependence
Drug: Buspirone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Psychopharmacology of Novel Medications for Cocaine Dependence - Buspirone

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • Cocaine-Stroop [ Time Frame: M, W, F @ 11:30 AM over 2 weeks ] [ Designated as safety issue: No ]
    The 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. The primary outcome measure is reaction times (RT), with attentional bias measured as the difference in RTs on cocaine vs. neutral words.

  • Risky decision making [ Time Frame: M, W, F @ 11 AM over 2 weeks ] [ Designated as safety issue: No ]
    The 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. Subjects start each test session with $5.00. End-of-session earnings can range from approximately +$12.00 to -$2.00. 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.


Secondary Outcome Measures:
  • ARCI [ Time Frame: M, W, F @ 10 time points, over 2 weeks ] [ Designated as safety issue: No ]
    Addiction Research Center Inventory. The ARCI short form [173] will be used. It is a 49-item true / false questionnaire that has been empirically-derived to assess five different factors, including euphoria, sedation, and dysphoria [174]. The PCAG scale has proven to be a sensitive measure of subjective effects in many studies administering stimulant drugs [174, 175]. We have employed it extensively in our laboratory [155, 175].

  • POMS [ Time Frame: M, W, F @ 10 time points, over 2 weeks ] [ Designated as safety issue: No ]
    Profile of Mood States. The POMS is a self-rating measure of current mood [176]. It consists of six subscales: depression, vigor, confusion, tension, anxiety, and fatigue. This instrument has been used in hundreds of studies in both clinical and healthy control populations, and has been demonstrated to be sensitive to a range of acute drug effects, including amphetamine [171], cocaine [38], and caffeine [108, 177]. We will use the 37-item short form of the POMS, which correlates highly with the full scale [178].

  • DEQ [ Time Frame: M, W, F @ 10 time points, over 2 weeks ] [ Designated as safety issue: No ]
    Drug Effects Questionnaire. The DEQ (e.g., [95]) is visual analog scale questionnaire (Drug Effects Questionnaire, or DEQ) that assesses the extent to which subjects experience four subjective states: "Feel Drug", "Feel High", "Like Drug", and "Want More".

  • VAS [ Time Frame: M, W, F @ 10 time points, over 2 weeks ] [ Designated as safety issue: No ]
    The VAS (e.g., [179]) presents 100-mm horizontal lines labeled with an adjective: "stimulated", "high", "anxious", "elated", "hungry", and "nauseated." The scale is anchored by "not at all" (0) on the left, and "extremely" (100) on the right.

  • cardiovascular [ Time Frame: M, W, F @ 10 time points, over 2 weeks ] [ Designated as safety issue: Yes ]
    Participants' heart rate, systolic and diastolic blood pressure will be recorded.


Estimated Enrollment: 36
Study Start Date: March 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Buspirone
week 1: Buspirone 30 mg BID weeks 2-3: Buspirone 45 mg BID
Drug: Buspirone
week 1 = 30 mg BID weeks 2-3 = 45 mg BID

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

  • < 18 or > 60 years of age
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01267292

Contacts
Contact: Scott D Lane, PhD 713-486-2535 Scott.D.Lane@uth.tmc.edu
Contact: Rolanda Johnson, BS 713-486-2639 Rolanda.Johnson@uth.tmc.edu

Locations
United States, Texas
Center for Neurobehavioral Research on Addiction, Department of Psychiatry & Behavioral Sciences, UTHSC-Hosuton Recruiting
Houston, Texas, United States, 77054
Contact: Scott D Lane, Ph.D.    713-486-2535    scott.d.lane@uth.tmc.edu   
Principal Investigator: Scott D Lane, Ph.D.         
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
Principal Investigator: Scott D Lane, Ph.D. The University of Texas Health Science Center, Houston
  More Information

No publications provided

Responsible Party: Scott Lane, Professor - Behavioral Sciences, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT01267292     History of Changes
Other Study ID Numbers: NIDA-P50-09262-Project2.1
Study First Received: December 24, 2010
Last Updated: May 19, 2014
Health Authority: United States: Federal Government

Keywords provided by The University of Texas Health Science Center, Houston:
cocaine dependence
psychopharmacology
attentional bias
risky decision making
buspirone
methylphenidate

Additional relevant MeSH terms:
Cocaine-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders
Buspirone
Cocaine
Anesthetics
Anesthetics, Local
Anti-Anxiety Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Serotonin Agents
Serotonin Receptor Agonists
Therapeutic Uses
Tranquilizing Agents
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on November 25, 2014