Cocaine Dependence
Conditions
Keywords
Cocaine Dependence, Substance Related Disorders
Brief summary
Doxazosin, an alpha 1-adrenergic receptor, may play an important role in cocaine addiction in humans. This study will evaluate the effectiveness of doxazosin in preventing drug relapse among cocaine dependent participants.
Detailed description
The NE system, especially the alpha 1-adrenergic receptor, may play an important role in cocaine addiction in humans. The results of this study will provide medical safety data on the duration of the induction schedule that will be optimal for attaining our target dose of 8 mg doxazosin daily and will guide future pharmacotherapy trials using Doxazosin or related alpha 1 receptor antagonists for cocaine addiction. This 17-week double-blind, placebo controlled clinical trial includes a 13 week medication trial (weeks 1-13) and up to 4 week washout period(weeks 14-17). Qualifying subjects will be randomized to receive Doxazosin 8 mg/day, or placebo during the study participation. Medication induction will occur at a rate of 2mg/week until 8mg/day target dose is achieved as follows: 1. Dox-Fast Group: Defined as participants reaching the target dose after a 4-week titration period. Participants will be stabilized on doxazosin or placebo over weeks 4-13 (for Dox-Fast group) 2. Dox-Slow Group: Defined as participants reaching the target dose after an 8-week titration period. Participants will be stabilized on doxazosin or placebo over weeks 8-13 (for Dox-Slow group) Both groups will be tapered off doxazosin or placebo over study weeks 14-17.
Interventions
DRUGDoxazosin
Medication induction occurred at a rate of 2mg/week until 8mg/day target dose was achieved as follows: 1. Dox-Fast Group: Defined as participants reaching the target dose after a 4-week titration period. Participants were stabilized on doxazosin or placebo over weeks 4-13 (for Dox-Fast group) 2. Dox-Slow Group: Defined as participants reaching the target dose after an 8-week titration period. Participants were stabilized on doxazosin or placebo over weeks 8-13 (for Dox-Slow group) Both doxazosin groups will be tapered off doxazosin or placebo over study weeks 14-17.
OTHERPlacebo
Participants will be administered a sugar pill to mimic the doxazosin active medication with administration being the same as the active medication.
Sponsors
National Institute on Drug Abuse (NIDA)
Baylor College of Medicine
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 64 Years
Healthy volunteers
No
Inclusion criteria
* Meets DSM-IV diagnosis criteria for cocaine dependence, as determined by self-reported use of cocaine at least once weekly for at least 1 month prior to study entry; a positive urine test for cocaine; and a score greater than 3 on the Severity of Dependence Scale * If female, willing to use contraception throughout the study
Exclusion criteria
* Meets DSM-IV diagnosis criteria for dependence on any drugs other than cocaine, or tobacco * Current major psychiatric illness, including schizophrenia, bipolar disorder, or other psychotic disorder * Current suicidal or homicidal ideation * Current use of a prescribed psychotropic medication that cannot be discontinued * History of or current major medical illness, including major heart, kidney, endocrine, or liver disorder; abnormal liver function (SGOT or SGPT levels three times greater than normal); or high blood pressure or low blood pressure * High risk factor for heart disease, seizure disorders, or any illness for which disulfiram or methadone treatment would be inadvisable * Currently taking metronidazole or clotrimazole * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Negative Urines | throughout the study - up to 17 weeks | cocaine urine toxicology samples were obtained thrice weekly and tested for the presence of the cocaine metabolite, benzoylecgonine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weeks of Abstinence | throughout the study - up to 17 weeks | Percentage of participants achieving 2 or more consecutive weeks of abstinence |
| # of Participants That Completed the Study | throughout the study - up to 17 weeks | Retention |
| Adverse Events | throughout study - upto 17 weeks | — |
Countries
United States
Participant flow
Recruitment details
Thirty-five subjects were randomized into the study, with 30 subjects returning and receiving at least one dose of medication.
Participants by arm
| Arm | Count |
|---|---|
| Doxazosin Slow Titration Medication induction occurred at a rate of 2mg/week until 8mg/day target dose was achieved as follows:
Dox-Slow Group: Participants reaching the target dose after an 8-week titration period. Participants were stabilized on doxazosin over weeks 8-13.
Participants were tapered off doxazosin or placebo over study weeks 14-17. | 8 |
| Doxazosin Fast Titration Medication induction occurred at a rate of 2mg/week until 8mg/day target dose was achieved as follows:
Dox-Fast Group: Participants reaching the target dose after a 4-week titration period. Participants were stabilized on doxazosin over weeks 4-13.
Participants were tapered off doxazosin or placebo over study weeks 14-17. | 9 |
| Placebo Participants received matched placebo during weeks 1-13.
Participants were tapered off placebo over study weeks 14-17. | 13 |
| Total | 30 |
Baseline characteristics
| Characteristic | Placebo | Total | Doxazosin Slow Titration | Doxazosin Fast Titration |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 30 Participants | 8 Participants | 9 Participants |
| Age, Continuous | 48.2 years STANDARD_DEVIATION 8.6 | 48 years STANDARD_DEVIATION 9 | 50.1 years STANDARD_DEVIATION 7.4 | 47.4 years STANDARD_DEVIATION 11 |
| Alcohol use - past 30 days | 7.85 days STANDARD_DEVIATION 9.89 | 8.5 days STANDARD_DEVIATION 8 | 6.63 days STANDARD_DEVIATION 3.77 | 10.11 days STANDARD_DEVIATION 9.55 |
| Cocaine use - past 30 days | 14.85 days STANDARD_DEVIATION 10.25 | 15 days STANDARD_DEVIATION 8.27 | 18.13 days STANDARD_DEVIATION 8.9 | 7.89 days STANDARD_DEVIATION 6.92 |
| Employment | 9 Participants | 22 Participants | 6 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 20 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 10 Participants | 1 Participants | 6 Participants |
| Region of Enrollment United States | 13 participants | 30 participants | 8 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 11 Participants | 26 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 9 | 0 / 13 |
| other Total, other adverse events | 2 / 8 | 3 / 9 | 3 / 13 |
| serious Total, serious adverse events | 0 / 8 | 0 / 9 | 0 / 13 |
Outcome results
Primary
Cocaine Negative Urines
cocaine urine toxicology samples were obtained thrice weekly and tested for the presence of the cocaine metabolite, benzoylecgonine
Time frame: throughout the study - up to 17 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOX-slow Group | Cocaine Negative Urines | 10 percentage of cocaine-negative urines |
| DOX-fast Group | Cocaine Negative Urines | 35 percentage of cocaine-negative urines |
| Placebo | Cocaine Negative Urines | 14 percentage of cocaine-negative urines |
Secondary
Adverse Events
Time frame: throughout study - upto 17 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOX-slow Group | Adverse Events | 26 events |
| DOX-fast Group | Adverse Events | 9 events |
| Placebo | Adverse Events | 23 events |
Secondary
# of Participants That Completed the Study
Retention
Time frame: throughout the study - up to 17 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DOX-slow Group | # of Participants That Completed the Study | 6 Participants |
| DOX-fast Group | # of Participants That Completed the Study | 6 Participants |
| Placebo | # of Participants That Completed the Study | 5 Participants |
Secondary
Weeks of Abstinence
Percentage of participants achieving 2 or more consecutive weeks of abstinence
Time frame: throughout the study - up to 17 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOX-slow Group | Weeks of Abstinence | 0 percentage of participants |
| DOX-fast Group | Weeks of Abstinence | 44 percentage of participants |
| Placebo | Weeks of Abstinence | 7 percentage of participants |