Cocaine Dependence
Conditions
Keywords
Cocaine-Related Disorders, Cocaine, Doxazosin, Cardiovascular Agents, Antihypertensive Agents, Adrenergic alpha-1 Receptor Antagonists, Adrenergic alpha-Antagonists, Adrenergic Antagonists, Molecular Mechanisms of Pharmacological Action, Neurotransmitter Agents, Therapeutic Uses, Pharmacologic Actions, Substance-Related Disorders
Brief summary
Cocaine use disorders affect approximately 1.5 million Americans annually. Currently, there are no US Food and Drug Administration approved medications for treatment of cocaine dependence; however, both animal and human studies suggest that medications affecting the noradrenergic system can reduce cocaine craving and use. The investigators will study the effect of doxazosin, an alpha-1 adrenergic antagonist, in reducing cocaine use and anxiety symptoms among cocaine-dependent individuals. In addition, the investigators will identify genetic subpopulations of participants who preferentially respond to the medication.
Detailed description
The noradrenergic system, especially the alpha 1-adrenergic receptor, may play an important role in cocaine addiction in humans. Doxazosin is a long-acting and selective alpha 1-adrenergic receptor blocker, which inhibits the binding of norepinephrine to alpha receptors in the autonomic nervous system. This study will evaluate the efficacy of doxazosin in reducing cocaine-using behavior in treatment seeking cocaine-dependent individuals, and will guide future pharmacotherapy trials using Doxazosin or related alpha 1 receptor antagonists for treatment of cocaine addiction. This 12-week double-blind, placebo controlled clinical trial will provide treatment for cocaine-dependent patients and includes a 8-week maintenance medication trial (weeks 3-10). At the end of this period, subjects will have a 2-week study medication taper (weeks 11-12). Qualifying subjects will be randomized to receive Doxazosin up to 8 mg/day or placebo. At the beginning of week 1, participants will receive Doxazosin, or placebo according to their randomized assignments, and are maintained on these agents through week 12. At the end of the study (weeks 11-12), participants will undergo discontinuation from active/inactive medication over a 2-week period. Subjects who wish to be transferred to an appropriate treatment program or research program will be referred to upon request, during the study weeks 11-12.
Interventions
DRUGDoxazosin
Doxazosin is initiated at 2 mg/wk, and titrated up to a maximum of 8 mg/day over approximately 4 weeks. Participants will be maintained on 8mg daily dosing until week 13. The subjects will undergo the discontinuation from the study medication during weeks 14 -15.
DRUGPlacebo
Matched placebo daily dosing
Sponsors
Baylor College of Medicine
VA Office of Research and Development
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
Yes
Inclusion criteria
1. Signed informed consent form and HIPAA authorization form 2. Subject is cooperative, understands the risks and benefits, and is willing and able to adhere to study requirements 3. Any race or ethnic origin 4. Diagnosis of cocaine-dependence according to DSM-IV criteria 5. Between the ages of 18 and 64 6. Must be current users of cocaine with self-reported use of cocaine within the last 90 days, or at least one cocaine-positive urine during screening. 7. Women of childbearing age are eligible to be included in the study if they have a negative pregnancy test at screening, agree to adequate contraception to prevent pregnancy, to have monthly pregnancy tests, and they understand the risk of fetal toxicity due to medication. 8. Must be in good general health as determined by self-report and/or CPRS-based medical history, general clinical examination conducted by a study physician, and lab tests. HIV testing will be recommended but is not required for participation in this study. 9. Motivated to discontinue or reduce cocaine use during the period of the study, as evidenced both by the judgment of the Investigator or designee and by the subject's compliance level with the requirement for attendance at clinic visits, such that weekly urine sample requirements for inclusion criteria are fully met.
Exclusion criteria
1. Current diagnosis of other drug dependence, especially alcohol or benzodiazepine dependence, or abuse (other than cocaine, tobacco, or cannabis) 2. Significant medical conditions (e.g., major cardiovascular, renal, endocrine, hepatic disorders) such as abnormal liver function (with laboratory findings of SGOT or SGPT greater than three times normal), hypotension, a current cardiac condition that in the opinion of the investigator would contraindicate Doxasozin treatment, and those having a high risk of cardiovascular disease, seizure disorders, or another significant underlying medical condition which would contraindicate Doxazosin treatment 3. Lifetime schizophrenia, bipolar disorder, or other psychotic disorders (excluding substance-induced psychotic disorders) 4. Actively considering plans of suicidality or homicidality 5. Women planning to become pregnant or breastfeed during the study, refusal to use a reliable form of birth control, or refusal of monthly pregnancy testing 6. Subjects who are prescribed certain anti-hypertension drugs (i.e. doxasozin) will be excluded because these medications may interact with Doxazosin's brain effects in reducing cocaine abuse 7. Subject has participated in another clinical trial or received any other investigational compound within 7 days prior to being randomized into this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Cocaine-positive Urines | Up to 12 weeks, or for the duration of the participant's involvement in the study | Over period of 12 weeks with 43 participants total (Doxazosin group = 22; Placebo group = 21), the overall percentage of cocaine positive urines per treatment group |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Doxazosin Doxazosin is a long-acting and selective alpha 1-NE blocker, which inhibits the binding of norepinephrine to alpha receptors in the autonomic nervous system.
Doxazosin (target 8mg/day) Induction - Week 1: 1mg once daily over days 1--3; 2mg once daily over days 4-7; Week 2: 4mg once daily over days 8-10; 8mg once daily over days 11-14; Week 3: 8mg once daily over days 15-end of week 10
Doxazosin tapered over weeks 11-12 -- Week 11: 4mg on Monday, Tuesday, Wednesday, and Thursday and 1mg for the duration of week 11. During week 12, subjects will receive 1mg on Monday, Tuesday, and Wednesday only. No further medication will be given for the remainder of week 12. | 22 |
| Placebo Matched placebo daily dosing.
Placebo: Matched placebo daily dosing | 21 |
| Total | 43 |
Baseline characteristics
| Characteristic | Doxazosin | Placebo | 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 | 22 Participants | 21 Participants | 43 Participants |
| Age, Continuous | 53.4 years | 54.9 years | 54.2 years |
| Lifetime cocaine years | 24.5 years | 24.1 years | 24.3 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 17 Participants | 36 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 | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United States | 22 Participants | 21 Participants | 43 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 20 Participants | 21 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 21 |
| other Total, other adverse events | 8 / 22 | 5 / 21 |
| serious Total, serious adverse events | 0 / 22 | 0 / 21 |
Outcome results
Primary
Percentage of Cocaine-positive Urines
Over period of 12 weeks with 43 participants total (Doxazosin group = 22; Placebo group = 21), the overall percentage of cocaine positive urines per treatment group
Time frame: Up to 12 weeks, or for the duration of the participant's involvement in the study
Population: Study population was comprised of 43 cocaine-dependent individuals who met inclusion criteria for this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxazosin | Percentage of Cocaine-positive Urines | 67.6 percentage of cocaine-positive urines |
| Placebo | Percentage of Cocaine-positive Urines | 69 percentage of cocaine-positive urines |