Cocaine DependencePhase 2NCT01267292
Psychopharmacology for Cocaine Dependence - Buspirone
A Phase 2 study testing Buspirone and Methylphenidate in people with Cocaine Dependence, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Cocaine Dependence
- What is being tested?
- Buspirone and Methylphenidate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Dec 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
About this study
Official title: 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.
Read the 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.
- Conditions
- Cocaine Dependence
- Being tested
- Buspirone, Placebo for Buspirone, Methylphenidate, Placebo for Methylphenidate
- Keywords
- cocaine dependence, psychopharmacology, attentional bias, risky decision making, buspirone, methylphenidate
- Medical subject headings
- Cocaine-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuspironeDrug
Also called Buspar
[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]
Placebo for BuspironeDrug
Also called corn starch
[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]
MethylphenidateDrug
Also called Ritalin
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 MethylphenidateDrug
Also called corn starch
[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)]
| Study group | Role | What they receive |
|---|---|---|
| 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)] Receives: 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)] Receives: Drug: Placebo for Buspirone; Drug: Methylphenidate; Drug: Placebo for Methylphenidate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
The ARCI short form 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. The PCAG scale has proven to be a sensitive measure of subjective effects in many studies administering stimulant drugs.
Measured: 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)
The mean score over all 44 time points is reported in this outcome measure (i.e., the summary score is reported). Each subject contributed 11 data points for each dose level of Methylphenidate (15mg, 30mg, 60mg, or 0mg), resulting in a total of 220 data points per dose level per arm.
The POMS is a self-rating measure of current mood, consisting of six subscales demonstrated to be sensitive to a range of acute drug effects, including amphetamine, cocaine, and caffeine. The six subscales are: depression, vigor, confusion, tension, anxiety, and fatigue. A 37-item short form of the POMS was used, which correlates highly with the full scale. The vigor subscale is reported, and the vigor subscale score ranges from 0 to 28, with 28 representing the highest score for that mood state. The higher the value, the worse the outcome.
Measured: 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)
The mean score over all 44 time points is reported in this outcome measure (i.e., the summary score is reported). Each subject contributed 11 data points for each dose level of Methylphenidate (15mg, 30mg, 60mg, or 0mg), resulting in a total of 220 data points per dose level per arm.
The DEQ is a visual analog scale questionnaire that assesses the extent to which subjects experience four subjective states: "Feel Drug," "Feel High," "Like Drug," and "Want More." The "Feel High" subscale is reported, and this subscale is scored on a visual analogue scale (scroll bar on computer screen) ranging from 0-100. 100 represents the highest score for that subjective state, and the higher the score, the worse the outcome.
Measured: 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)
The mean score over all 44 time points is reported in this outcome measure (i.e., the summary score is reported). Each subject contributed 11 data points for each dose level of Methylphenidate (15mg, 30mg, 60mg, or 0mg), resulting in a total of 220 data points per dose level per arm.
The VAS presents 100-mm horizontal lines labeled with an adjective: "stimulated," "high," "anxious," "elated," "hungry," and "nauseated." The "elated" subscale is reported, and this sub scale is anchored by "not at all" (0) on the left and "extremely" (100) on the right, with a score range of 0-100. The higher the score, the worse the outcome.
Measured: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
Heart Rate
The mean score over all 44 time points is reported in this outcome measure (i.e., the summary score is reported). Each subject contributed 11 data points for each dose level of Methylphenidate (15mg, 30mg, 60mg, or 0mg), resulting in a total of 220 data points per dose level per arm.
Heart rate is the measure of heart beats per minute.
Measured: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
Systolic Blood Pressure
The mean score over all 44 time points is reported in this outcome measure (i.e., the summary score is reported). Each subject contributed 11 data points for each dose level of Methylphenidate (15mg, 30mg, 60mg, or 0mg), resulting in a total of 220 data points per dose level per arm.
Systolic blood pressure is the amount of pressure in the arteries during contraction of the heart muscle.
Measured: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
Diastolic Blood Pressure
The mean score over all 44 time points is reported in this outcome measure (i.e., the summary score is reported). Each subject contributed 11 data points for each dose level of Methylphenidate (15mg, 30mg, 60mg, or 0mg), resulting in a total of 220 data points per dose level per arm.
Diastolic blood pressure is the blood pressure when the heart muscle is between beats.
Measured: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
Rapid Response Inhibition as Assessed by the Immediate Memory Task (IMT)
Subjects are required to respond selectively to a series of stimuli (e.g., numbers) presented briefly for 500 ms with a 500 ms intertrial interval (ITI). Increases in false alarm rates are interpreted as failures in response inhibition. Five digit numbers are presented on a computer screen every 500 ms sec. Subjects are instructed to respond when the first number of a set was repeated. A "hit" response is scored when a subject correctly responds. Distracters consist of five-digit numbers that are completely different from the first, and numbers in which four of the five digits match the original, with the non-matching number occurring randomly across the five digit places. A response to the number with 4 of 5 digits correct is scored as a "false alarm." The a-prime value reflects the ability of the participant to discriminate between signal (Go stimulus) and noise (No-Go stimulus) and ranges from 0.5 (chance level) to 1 (perfect discrimination).
Measured: baseline
Rapid Response Inhibition as Assessed by the Immediate Memory Task (IMT)
Subjects are required to respond selectively to a series of stimuli (e.g., numbers) presented briefly for 500 ms with a 500 ms intertrial interval (ITI). Increases in false alarm rates are interpreted as failures in response inhibition. Five digit numbers are presented on a computer screen every 500 ms sec. Subjects are instructed to respond when the first number of a set was repeated. A "hit" response is scored when a subject correctly responds. Distracters consist of five-digit numbers that are completely different from the first, and numbers in which four of the five digits match the original, with the non-matching number occurring randomly across the five digit places. A response to the number with 4 of 5 digits correct is scored as a "false alarm." The a-prime value reflects the ability of the participant to discriminate between signal (Go stimulus) and noise (No-Go stimulus) and ranges from 0.5 (chance level) to 1 (perfect discrimination).
Measured: Thursday of week 1
Rapid Response Inhibition as Assessed by the Immediate Memory Task (IMT)
Subjects are required to respond selectively to a series of stimuli (e.g., numbers) presented briefly for 500 ms with a 500 ms intertrial interval (ITI). Increases in false alarm rates are interpreted as failures in response inhibition. Five digit numbers are presented on a computer screen every 500 ms sec. Subjects are instructed to respond when the first number of a set was repeated. A "hit" response is scored when a subject correctly responds. Distracters consist of five-digit numbers that are completely different from the first, and numbers in which four of the five digits match the original, with the non-matching number occurring randomly across the five digit places. A response to the number with 4 of 5 digits correct is scored as a "false alarm." The a-prime value reflects the ability of the participant to discriminate between signal (Go stimulus) and noise (No-Go stimulus) and ranges from 0.5 (chance level) to 1 (perfect discrimination).
Measured: Monday of week 4
Reversal Learning as Assessed by Number of Perseverative Errors on the Reversal Learning Task
The task is a rapid-presentation, probablistic gain/loss design. Reversal learning is assessed by means of a simple computerized card game. The paradigm utilizes a visual discrimination task where subjects have to learn to respond to outcome contingencies between two stimuli (high probability gain/low probability loss vs. low probability gain/high probability loss). At an unsignaled time point halfway into testing, the contingencies are reversed; the losing card becomes the winning card and the winning card becomes the losing one. Visual feedback regarding win or loss ($0.20) is provided after each trial and the cumulative total gained/lost is also shown. Using trial-and-error feedback, subjects have to discover which of the two patterns is correct and are instructed to win as much money as possible. The duration of the task is approximately 10 minutes, consisting of 80 trials.
Measured: baseline
Reversal Learning as Assessed by Number of Perseverative Errors on the Reversal Learning Task
The task is a rapid-presentation, probablistic gain/loss design. Reversal learning is assessed by means of a simple computerized card game. The paradigm utilizes a visual discrimination task where subjects have to learn to respond to outcome contingencies between two stimuli (high probability gain/low probability loss vs. low probability gain/high probability loss). At an unsignaled time point halfway into testing, the contingencies are reversed; the losing card becomes the winning card and the winning card becomes the losing one. Visual feedback regarding win or loss ($0.20) is provided after each trial and the cumulative total gained/lost is also shown. Using trial-and-error feedback, subjects have to discover which of the two patterns is correct and are instructed to win as much money as possible. The duration of the task is approximately 10 minutes, consisting of 80 trials.
Measured: Thursday of week 1
Reversal Learning as Assessed by Number of Perseverative Errors on the Reversal Learning Task
The task is a rapid-presentation, probablistic gain/loss design. Reversal learning is assessed by means of a simple computerized card game. The paradigm utilizes a visual discrimination task where subjects have to learn to respond to outcome contingencies between two stimuli (high probability gain/low probability loss vs. low probability gain/high probability loss). At an unsignaled time point halfway into testing, the contingencies are reversed; the losing card becomes the winning card and the winning card becomes the losing one. Visual feedback regarding win or loss ($0.20) is provided after each trial and the cumulative total gained/lost is also shown. Using trial-and-error feedback, subjects have to discover which of the two patterns is correct and are instructed to win as much money as possible. The duration of the task is approximately 10 minutes, consisting of 80 trials.
Measured: Monday of week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2010 (estimated)
- Study startMar 2011
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cocaine DependenceStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Scott Lane, The University of Texas Health Science Center, Houston
- Investigators
- Scott D Lane, Ph.D., Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01267292
- Sponsor's protocol ID
- NIDA-P50-09262-Project2.1
- Status last verified
- May 2017
- First submitted
- 24 Dec 2010
- Last updated
- 4 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psychopharmacology of Novel Medications for Cocaine Dependence - Buspirone
- ClinicalTrials.gov ID
- NCT01267292
- Acronym / sponsor ID
- NIDA-P50-09262-Project2.1
- Conditions
- Cocaine Dependence
- Keywords
- cocaine dependence, psychopharmacology, attentional bias, risky decision making, buspirone, methylphenidate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 28 Dec 2010 (estimated)
- Results
- Posted 4 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Buspirone plus Methylphenidate | Experimental | Drug: Buspirone, Drug: Methylphenidate, Drug: Placebo for 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)] |
| Placebo for Buspirone plus Methylphenidate | Placebo comparator | Drug: Placebo for Buspirone, Drug: Methylphenidate, Drug: Placebo for 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)] |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BuspironeAlso: Buspar[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] | Drug | Buspirone plus Methylphenidate |
| Placebo for BuspironeAlso: corn starch[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] | Drug | Placebo for Buspirone plus Methylphenidate |
| MethylphenidateAlso: RitalinMethylphenidate 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)] | Drug | Buspirone plus Methylphenidate, Placebo for Buspirone plus Methylphenidate |
| Placebo for MethylphenidateAlso: corn starch[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)] | Drug | Buspirone plus Methylphenidate, Placebo for Buspirone plus Methylphenidate |
Primary outcome
Attentional Bias as Assessed by Score on the Stroop Task
Time frame: 1 time a day on Wednesday and Friday of week 2; 1 time a day on Monday and Wednesday of week 3
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.
Risky Decision Making as Assessed by Score on the Risky Decision Making Task
Time frame: 1 time a day on Wednesday and Friday of week 2; 1 time a day on Monday and Wednesday of week 3
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.
13 secondary outcomes
Subjective Effects as Assessed by the Addiction Research Center Inventory (ARCI)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
Heart Rate
Time frame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
Systolic Blood Pressure
Time frame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
Diastolic Blood Pressure
Time frame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
Rapid Response Inhibition as Assessed by the Immediate Memory Task (IMT)
Time frame: baseline
Rapid Response Inhibition as Assessed by the Immediate Memory Task (IMT)
Time frame: Thursday of week 1
Rapid Response Inhibition as Assessed by the Immediate Memory Task (IMT)
Time frame: Monday of week 4
Reversal Learning as Assessed by Number of Perseverative Errors on the Reversal Learning Task
Time frame: baseline
Reversal Learning as Assessed by Number of Perseverative Errors on the Reversal Learning Task
Time frame: Thursday of week 1
Reversal Learning as Assessed by Number of Perseverative Errors on the Reversal Learning Task
Time frame: Monday of week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Cocaine Dependence
Recruiting
rTMS and Cognitive-behavioral Therapy for Cocaine Use Disorder
Cocaine Use, Cocaine Dependence
Not yet recruiting
QAIAx - SGI/SI Smart Health Cities: Microcity Enclave Program (Quantum SI/AGI Agency a/k/a AI City Hall Project - UPSTO App Nos. 64/074,526, 64/063,557, 64/105,164, 63/903,181, 63/729,428, 64/125,360; USPTO EO 9424 Assignment ID: 2101042 / ARN: REEL/FRAME: 76481/0026 - OUSD-R&E, Department of War)
Asperger's Disorder, Asperger Disorder
Recruiting
Transcranial Direct Current Stimulation (tDCS) for Treatment of Substance Use Disorder
Cocaine Use Disorder, Cocaine Dependence
RecruitingPhase 1
Safety Study of a Disrupted Adenovirus (Ad) Serotype Cocaine Vaccine for Cocaine-dependent Individuals
Cocaine Dependence
Active, not recruitingPhase 1
AAV8-hCocH for Cocaine Use Disorder
Cocaine Dependence, in Remission
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott D Lane, Ph.D. principal investigator
The University of Texas Health Science Center, Houston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Buspirone and Methylphenidate in people with Cocaine Dependence, run by The University of Texas Health Science Center, Houston at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Attentional Bias as Assessed by Score on the Stroop Task (time frame: 1 time a day on Wednesday and Friday of week 2; 1 time a day on Monday and Wednesday of week 3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2017.