Psychopharmacology for Cocaine Dependence - Buspirone

This study is currently recruiting participants.
Verified May 2013 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 2, 2013
Last verified: May 2013

December 24, 2010
May 2, 2013
March 2011
July 2013   (final data collection date for primary outcome measure)
  • 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.
Same as current
Complete list of historical versions of study NCT01267292 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Psychopharmacology for Cocaine Dependence - Buspirone
Psychopharmacology of Novel Medications for Cocaine Dependence - Buspirone

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Basic Science
Cocaine Dependence
Drug: Buspirone
week 1 = 30 mg BID weeks 2-3 = 45 mg BID
Experimental: Buspirone
week 1: Buspirone 30 mg BID weeks 2-3: Buspirone 45 mg BID
Intervention: Drug: Buspirone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
36
July 2013
July 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 60 Years
No
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
United States
 
NCT01267292
NIDA-P50-09262-Project2.1
Yes
Scott Lane, The University of Texas Health Science Center, Houston
The University of Texas Health Science Center, Houston
Not Provided
Principal Investigator: Scott D Lane, Ph.D. The University of Texas Health Science Center, Houston
The University of Texas Health Science Center, Houston
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP