Cocaine Dependence
Conditions
Keywords
Cocaine, Crack, Buspirone, Relapse Prevention
Brief summary
The purpose of this study is to evaluate whether or not buspirone is effective in preventing relapse in cocaine-dependent adults in inpatient/residential treatment who are planning to enter outpatient treatment upon inpatient/residential discharge.
Detailed description
The primary objective is to evaluate the efficacy of buspirone, relative to placebo, in preventing relapse in cocaine-dependent adults in inpatient/residential treatment who are planning to enter outpatient treatment upon inpatient/residential discharge. Secondary objectives include evaluating the impact of buspirone, relative to placebo, on other drug-abuse outcomes and on factors that may mediate buspirone's efficacy as a relapse-prevention treatment.
Interventions
DRUGBuspirone
Study participants will be randomly assigned to receive either buspirone or matching placebo. Following dose escalation, the target at study day 10 is to achieve the highest tolerated dose not exceeding 60 mg. Participants who are unable to reach the 60 mg dose or who need to be reduced from 60 mg due to tolerability will be maintained on 15 mg, 30 mg, or 45 mg, whichever is the highest dose tolerated.
DRUGPlacebo
Study participants will be randomly assigned to receive either buspirone or matching placebo. Placebo tablets will be identical in color and size to the buspirone tablets.
Sponsors
National Institute on Drug Abuse (NIDA)
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. be 18 years of age or older 2. be able to understand the study, and having understood, provide written informed consent in English 3. meet DSM-IV-TR diagnostic criteria for current (within the last 12 months) dependence for cocaine, must self-report having used crack cocaine a minimum of four times in the 28 days prior to inpatient/residential admission, and must report that their typical pattern of use is at least once a week 4. have a willingness to comply with all study procedures and medication instructions 5. be enrolled in an inpatient/residential program at a participating CTP, scheduled to be in inpatient/residential treatment for 12-19 days when randomized, and planning to enroll in local outpatient treatment through the end of the active treatment phase (i.e., study week 15) 6. if female and of child bearing potential, agree to use one of the following methods of birth control: * oral contraceptives * contraceptive patch * barrier (diaphragm or condom) * intrauterine contraceptive system * levonorgestrel implant * medroxyprogesterone acetate contraceptive injection * complete abstinence from sexual intercourse * hormonal vaginal contraceptive ring
Exclusion criteria
1. meet DSM-IV-TR diagnostic criteria for current (within the last 12 months) opioid dependence 2. have a medical or psychiatric condition that, in the judgment of the study physician, would make study participation unsafe or which would make treatment compliance difficult. Medical conditions that may compromise participant safety or study conduct include, but are not limited to: * AIDS according to the current CDC criteria for AIDS * liver function tests greater than 3X upper limit of normal * serum creatinine greater than 2 mg/dL 3. have a psychiatric disorder requiring continued treatment with a psychotropic medication 4. have a known or suspected hypersensitivity to buspirone 5. be pregnant or breastfeeding 6. have used any of the following medications within 14 days of randomization: monoamine oxidase (MAO) inhibitors such as phenelzine (Nardil), selegiline (Eldepryl), isocarboxazid (Marplan), or tranylcypromine (Parnate) 7. be taking any medications which, in the judgment of the study physician, may produce interactions with buspirone that are sufficiently dangerous so as to exclude the patient from participating in the study. Alternatively, the study physician, in consultation with the patient and his or her physician, may elect to withdraw the patient from the problem medications before randomization. Some of the possible interactions are discussed in section 8.8. 8. be anyone who, in the judgment of the investigator, would not be expected to complete the study protocol (e.g., due to relocation from the clinic area, probable incarceration, etc.) 9. be a significant suicidal/homicidal risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Days of Continuous Cocaine Abstinence | study week 16 | The primary outcome measure selected for the present two-stage protocol is the maximum days of continuous cocaine abstinence during study weeks 4-15. The Timeline Follow-back (TLFB) procedure (Sobell and Sobell, 1992; Fals-Stewart, 2000) will be used to assess the participants' self-reported use of substances for each day of the study. A rapid UDS system that screens for drugs of abuse will be used to analyze the urine samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine-use Days | study week 16 | Cocaine use days during days 22-105 as assessed by UDS and self-report combined with no imputation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Buspirone Plus TAU Buspirone titrated to 60 mg/day for the 15-week active study
Buspirone: Study participants will be randomly assigned to receive either buspirone or matching placebo. Following dose escalation, the target at study day 10 is to achieve the highest tolerated dose not exceeding 60 mg. Participants who are unable to reach the 60 mg dose or who need to be reduced from 60 mg due to tolerability will be maintained on 15 mg, 30 mg, or 45 mg, whichever is the highest dose tolerated. | 35 |
| Placebo Plus TAU Placebo taken daily for the 15-week active study
Placebo: Study participants will be randomly assigned to receive either buspirone or matching placebo. Placebo tablets will be identical in color and size to the buspirone tablets. | 27 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Buspirone Plus TAU | Placebo Plus TAU | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 27 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 27 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 19 Participants | 45 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 6 Participants | 14 Participants |
| Region of Enrollment United States | 35 participants | 27 participants | 62 participants |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 23 Participants |
| Sex: Female, Male Male | 24 Participants | 15 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 35 | 11 / 27 |
| serious Total, serious adverse events | 3 / 35 | 0 / 27 |
Outcome results
Primary
Maximum Days of Continuous Cocaine Abstinence
The primary outcome measure selected for the present two-stage protocol is the maximum days of continuous cocaine abstinence during study weeks 4-15. The Timeline Follow-back (TLFB) procedure (Sobell and Sobell, 1992; Fals-Stewart, 2000) will be used to assess the participants' self-reported use of substances for each day of the study. A rapid UDS system that screens for drugs of abuse will be used to analyze the urine samples.
Time frame: study week 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buspirone Plus TAU | Maximum Days of Continuous Cocaine Abstinence | 42.9 Days | Standard Deviation 30.83 |
| Placebo Plus TAU | Maximum Days of Continuous Cocaine Abstinence | 46.6 Days | Standard Deviation 31.03 |
Secondary
Cocaine-use Days
Cocaine use days during days 22-105 as assessed by UDS and self-report combined with no imputation
Time frame: study week 16
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buspirone Plus TAU | Cocaine-use Days | 0.153 proportion of cocaine use days |
| Placebo Plus TAU | Cocaine-use Days | 0.134 proportion of cocaine use days |