Cocaine Dependence, Cocaine Withdrawal
Conditions
Keywords
cocaine dependence, cocaine withdrawal
Brief summary
This study examines whether carvedilol prolongs abstinence in recently abstinent cocaine dependent participants.
Interventions
DRUGcontrolled release carvedilol
carvedilol (Coreg CR) 80 mg/day in once daily dosing for 12 weeks followed by a 2-week taper
DRUGPlacebo
Placebo
Sponsors
National Institute on Drug Abuse (NIDA)
Baylor College of Medicine
University of Arkansas
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 45 Years
Healthy volunteers
No
Inclusion criteria
* 18-45 years old * Cocaine dependence, as assessed by the substance abuse section of the Structured Clinical Interview for DSM-IV. * At least weekly self-reported cocaine use during a preceding three month period * Urine toxicology screen positive for cocaine or cocaine metabolite * Women of childbearing age must have a negative pregnancy test, agree to adequate contraception to prevent pregnancy during the study, agree to monthly pregnancy testing and not be nursing
Exclusion criteria
* Suicide attempts within the past 12 months or suicidal ideations or psychotic symptoms in the past 6 months as determined by a study physician. * Current opioid, alcohol or sedative physical dependence or amphetamine dependence. * Major cardiovascular disorder that contraindicates study participation (e.g., history of myocardial infarction, stroke, congestive heart failure, cardiac arrhythmia, significant hypertension \[i.e., \>170 SBP or \>110 DBP\] or an unstable medical condition (e.g., untreated bacterial infection) as determined by the study physician. * Asthma or chronic obstructive pulmonary disease. * History of schizophrenia, or bipolar type I disorder. * Use of medications that would be expected to have major interaction with carvedilol (e.g., rifampin, cimetidine, digoxin, diuretics). * Medical contraindication to receiving carvedilol (e.g., diabetes, severe bradycardia, bronchial asthma or other bronchospastic condition, 2nd or 3rd degree AV block, sick sinus rhythm, severe hepatic impairment, documented hypersensitivity to carvedilol). * Patients currently taking selective serotonin re-uptake inhibitors, antipsychotics and antidepressants (e.g., amitriptyline and imipramine). * Liver function tests (i.e., liver enzymes) greater than three times normal levels. * Systolic blood pressure \> 170 mmHg or \< 90 mmHg, diastolic blood pressure \> 110 mmHg or \< 60 mmHg, or heart rate of \> 110 beats/min or \< 55 beats/min. Supine blood pressure of 100/65 mm Hg or lower, a seated blood pressure of 90/60 mm Hg or lower, or an orthostatic change of \>20mm Hg systolic or 10 mm Hg diastolic on standing. * Participants with estimated glomerular filtration rate \< 30 ml/min. * Pregnant or nursing female.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urine Toxicology Screens | based on thrice weekly urine results during the 10-week outpatient phase | Treatment Effectiveness Score, defined by the # of cocaine negative urines during the outpatient phase of the study divided by the total number of urine samples (30) and then multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retention | 12 weeks | number of weeks each participant is on study protocol |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: Placebo | 15 |
| Carvedilol Controlled Release controlled release carvedilol (Coreg CR) at 80 mg/day in once daily dosing
controlled release carvedilol: carvedilol (Coreg CR) 80 mg/day in once daily dosing for 12 weeks followed by a 2-week taper | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Outpatient Participation (Weeks 3-10) | Lost to Follow-up | 7 | 3 |
| Outpatient Participation (Weeks 3-10) | Use of contraindicated med: PI term | 1 | 0 |
| Outpatient Participation (Weeks 3-10) | Withdrawal by Subject | 2 | 2 |
| Residential Facility (Weeks 1-2) | BP outside of study parameters | 0 | 3 |
| Residential Facility (Weeks 1-2) | Protocol Violation | 0 | 1 |
| Residential Facility (Weeks 1-2) | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | Carvedilol Controlled Release | 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 | 15 Participants | 15 Participants | 30 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 | 14 Participants | 12 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 1 Participants | 3 Participants | 4 Participants |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 7 Participants |
| Sex: Female, Male Male | 14 Participants | 9 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 15 | 13 / 15 |
| serious Total, serious adverse events | 0 / 15 | 1 / 15 |
Outcome results
Primary
Urine Toxicology Screens
Treatment Effectiveness Score, defined by the # of cocaine negative urines during the outpatient phase of the study divided by the total number of urine samples (30) and then multiplied by 100.
Time frame: based on thrice weekly urine results during the 10-week outpatient phase
Population: Those who completed the residential facility and attended at least one outpatient clinic visit to complete assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Urine Toxicology Screens | 38.33 percentage of cocaine negative urines | Standard Deviation 35.23 |
| Carvedilol Controlled Release | Urine Toxicology Screens | 41.85 percentage of cocaine negative urines | Standard Deviation 40.73 |
p-value: 0.05t-test, 2 sided
Secondary
Retention
number of weeks each participant is on study protocol
Time frame: 12 weeks
Population: Those eligible participants who entered the residential facility and received at least one dose of study medication. One person in the carvedilol group is excluded from all analyses due to not meeting inclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Retention | 5.70 Weeks | Standard Deviation 4.04 |
| Carvedilol Controlled Release | Retention | 5.28 Weeks | Standard Deviation 5 |
p-value: 0.05t-test, 2 sided