Methamphetamine or Cocaine Dependence
Conditions
Brief summary
Psychostimulant dependence is a major public health problem and no medications have been shown to be very effective in treating this disorder. Thus, the investigators wish to study whether a blood pressure drug thought to reduce drug craving through its interaction at particular adrenergic receptors - doxazosin - can dredge cocaine use relative to placebo in psychostimulant dependent participants enrolled in an 8-week, randomized, double blind, placebo-controlled outpatient clinical trial. Our hypothesis is that doxazosin will reduce cocaine use relative to placebo in psychostimulant dependent participants.
Interventions
DRUGDoxazosin extended release
initially maintained on doxazosin extended release 4 mg once a day for 7 days, then the dose is increased to 8 mg once per day for the duration of the trial.
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
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 18-55 years old * Methamphetamine OR cocaine dependence, as assessed by the substance abuse section of the Structured Clinical Interview for DSM-IV. * At least weekly self-reported methamphetamine OR cocaine use during a preceding three month period * Urine toxicology screen positive for methamphetamine or methamphetamine metabolite OR 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 dependence on both cocaine and methamphetamine * 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. * Any history or evidence suggestive of seizure disorder or brain injury * Subjects needing or planning cataract surgery. * History of schizophrenia, major depression, or bipolar type I disorder * Organic brain disease or dementia assessed by physician * Use of medications that would be expected to have major interaction with doxazosin (e.g. atanazavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole or any other potent 3A4 inhibitor.,) * Any previous medically adverse reaction to methamphetamine or cocaine, including loss of consciousness, chest pain, or epileptic seizure * Medical contraindication to receiving doxazosin (e.g. liver problems or allergies to other to other quinazolines such as prazosin or terazosin) * Severe gastrointestinal disorder as determined by physician * 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. * Have evidence of untreated or unstable medical illness including: neuroendocrine, autoimmune, renal, hepatic, or active infectious disease * Have symptomatic HIV or are taking antiretroviral medication * Have asthma or currently use theophylline or other sympathomimetics * Participants with estimated glomerular filtration rate \< 30 ml/min. * Pregnant or nursing female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Psychostimulant-positive Urines Over Time | twice-weekly urine samples (8 weeks) | Urine samples positive for methamphetamine or cocaine via twice-weekly urine drug screens. Weekly urine results data were averaged within subjects and the mean proportion across subjects within each group was calculated for graphic representation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Doxazosin Doxazosin extended release will be administered initially at 4 mg/day. On day 8 the dose is increased to 8 mg/day and the participant is maintained on the study until the end of the trial.
Doxazosin extended release: initially maintained on doxazosin extended release 4 mg once a day for 7 days, then the dose is increased to 8 mg once per day for the duration of the trial. | 11 |
| Placebo Participants will be maintained on placebo (cellulose) throughout the trial.
Doxazosin extended release: initially maintained on doxazosin extended release 4 mg once a day for 7 days, then the dose is increased to 8 mg once per day for the duration of the trial. | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Blood Pressure outside study parameters | 2 | 0 |
| Overall Study | Lost to Follow-up | 5 | 8 |
| Overall Study | non study related adverse event | 1 | 0 |
| Overall Study | was arrested and put in jail | 0 | 1 |
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 | 11 Participants | 11 Participants | 22 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 | 5 Participants | 4 Participants | 9 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 | 6 Participants | 7 Participants | 13 Participants |
| Region of Enrollment United States | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 11 | 4 / 11 |
| serious Total, serious adverse events | 1 / 11 | 0 / 11 |
Outcome results
Primary
Change in Psychostimulant-positive Urines Over Time
Urine samples positive for methamphetamine or cocaine via twice-weekly urine drug screens. Weekly urine results data were averaged within subjects and the mean proportion across subjects within each group was calculated for graphic representation.
Time frame: twice-weekly urine samples (8 weeks)
Population: Those eligible participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Doxazosin | Change in Psychostimulant-positive Urines Over Time | Week 1 (N=10, 11) | .6 proportion of psychostimulant-pos urines | Standard Deviation 0.52 |
| Doxazosin | Change in Psychostimulant-positive Urines Over Time | Week 2 (N=7, 8) | .79 proportion of psychostimulant-pos urines | Standard Deviation 0.39 |
| Doxazosin | Change in Psychostimulant-positive Urines Over Time | Week 3 (N=6, 5) | .58 proportion of psychostimulant-pos urines | Standard Deviation 0.49 |
| Doxazosin | Change in Psychostimulant-positive Urines Over Time | Week 4 (N=6, 4) | .75 proportion of psychostimulant-pos urines | Standard Deviation 0.42 |
| Doxazosin | Change in Psychostimulant-positive Urines Over Time | Week 5 (N=4, 4) | .5 proportion of psychostimulant-pos urines | Standard Deviation 0.41 |
| Doxazosin | Change in Psychostimulant-positive Urines Over Time | Week 6 (N=4, 3) | .63 proportion of psychostimulant-pos urines | Standard Deviation 0.25 |
| Doxazosin | Change in Psychostimulant-positive Urines Over Time | Week 7 (N=4, 3) | 1 proportion of psychostimulant-pos urines | Standard Deviation 0 |
| Doxazosin | Change in Psychostimulant-positive Urines Over Time | Week 8 (N=3, 2) | .83 proportion of psychostimulant-pos urines | Standard Deviation 0.29 |
| Placebo | Change in Psychostimulant-positive Urines Over Time | Week 8 (N=3, 2) | .25 proportion of psychostimulant-pos urines | Standard Deviation 0.35 |
| Placebo | Change in Psychostimulant-positive Urines Over Time | Week 1 (N=10, 11) | .41 proportion of psychostimulant-pos urines | Standard Deviation 0.49 |
| Placebo | Change in Psychostimulant-positive Urines Over Time | Week 5 (N=4, 4) | .25 proportion of psychostimulant-pos urines | Standard Deviation 0.29 |
| Placebo | Change in Psychostimulant-positive Urines Over Time | Week 2 (N=7, 8) | .25 proportion of psychostimulant-pos urines | Standard Deviation 0.38 |
| Placebo | Change in Psychostimulant-positive Urines Over Time | Week 7 (N=4, 3) | 0 proportion of psychostimulant-pos urines | Standard Deviation 0 |
| Placebo | Change in Psychostimulant-positive Urines Over Time | Week 3 (N=6, 5) | .4 proportion of psychostimulant-pos urines | Standard Deviation 0.55 |
| Placebo | Change in Psychostimulant-positive Urines Over Time | Week 6 (N=4, 3) | 0 proportion of psychostimulant-pos urines | Standard Deviation 0 |
| Placebo | Change in Psychostimulant-positive Urines Over Time | Week 4 (N=6, 4) | .5 proportion of psychostimulant-pos urines | Standard Deviation 0.58 |
Comparison: The analysis was applied to urine data obtained at all time points during weeks 1-8.p-value: 0.05Regression, Logistic