Complementary Combination Therapy for Cocaine Dependence
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Subjective effects (VAS) - change from baseline over 60 minutes
研究概览
简要总结
The investigators will assess the impact of treatment with doxazosin and modafinil, alone and in combination, on the subjective and reinforcing effects of cocaine in non-treatment-seeking, cocaine-dependent volunteers. The investigators will use a hybrid design in which participants will be randomized into two groups: placebo and doxazosin 8 mg/d. They will remain in their assigned group for the duration of the study. After titrating doxazosin to the target dose, study procedures will be completed three times, once during treatment with each dose of modafinil (0, 200, and 300 mg/d), in pseudo-random order such that 200 mg precedes 300 mg).
详细描述
During a screening session participants will provide buccal swab for genetics testing, as preliminary data shows that effects of cocaine and of doxazosin are impacted significantly by the genotype at ADRA1A, in that those with the CC genotype respond robustly to both cocaine and doxazosin whereas those with the CT genotype do not. Participants will be enrolled regardless of genotype, though the investigators plan to retrospectively exclude those with the rare TT genotype.
During screening, the investigators will collect participants' demographic and medical histories, conduct a physical exam, and record an ECG. A trained assistant will administer the MINI to collect diagnostic data. The investigators will draw blood and for CBC and a comprehensive metabolic panel including electrolytes, liver function tests (total bilirubin, ALT, AST, and alkaline phosphatase) and renal function tests (creatinine and BUN).
All applicants for study participation will receive counseling as part of their participation, and will be advised that treatment for drug abuse is indicated and available. Applicants not participating in the study will receive treatment referral information as appropriate. At completion of their participation, study subjects will again be advised that treatment is indicated and available, and will be given treatment referral information and assistance.
General Procedures Participants will report to the research commons three-times-weekly during the 11 day doxazosin titration period. They will be allowed to miss up to 3 visits but will be discontinued if they miss more that 3 visits. At the initial screening visit, restrictions on use of alcohol, drugs of abuse, and medications will be reviewed. All subjects will be required to sign a written statement that they will abstain from all psychostimulants throughout the duration of their participation in the trial.
After determining that volunteers meet inclusion and exclusion criteria, participants will receive screening doses of cocaine (0, 20, 40 mg, IV, constrained such that 20 mg precedes 40 mg). To be retained in the study participants must report a change in ratings of "high" of at least 20 points from before to following the 40 mg dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be English-speaking volunteers who are not seeking treatment at the time of the study. We require proficiency in English to ensure good communication with staff
- •Be aged between 18 and 55 years
- •Meet DSM-IV TR criteria for cocaine dependence using the MINI
- •Have a self-reported history of using cocaine by the IV or smoked route
- •Have vital signs as follows: resting pulse between 50 and 95 bpm, BP between 90-150 mmHg systolic and 45-95 mmHg diastolic
- •Have hematology and chemistry laboratory tests that are within reference limits (±10%), with the following exceptions: (a) liver function tests (total bilirubin, ALT, AST, and alkaline phosphatase) <3× the upper limit of normal and (b) kidney function tests (creatinine and BUN) <2× the upper limit of normal
- •Have a baseline ECG that demonstrates clinically normal sinus rhythm, clinically normal conduction, and no clinically significant arrhythmias
- •Have a medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the principal investigator
排除标准
- •Have any history or evidence suggestive of seizure disorder or brain injury
- •Have any previous medically adverse reaction to cocaine, including loss of consciousness, chest pain, or epileptic seizure
- •Meet criteria for current dependence on any drug other than cocaine or nicotine
- •Have neurological or psychiatric disorders, such as:
- •psychosis, bipolar illness or major depression as assessed by MINI;
- •organic brain disease or dementia assessed by clinical interview;
- •history of any psychiatric disorder that would require ongoing treatment or that would make study compliance difficult;
- •and history of suicide attempts within the past year and/or current suicidal ideation/plan
- •Have evidence of clinically significant heart disease or hypertension, as determined by the PI
- •Have a family history in first-degree relatives of early cardiovascular morbidity or mortality, as determined by the PI
- •Have evidence of untreated or unstable medical illness including neuroendocrine, autoimmune, renal, hepatic, or active infectious disease
- •Have HIV and are currently symptomatic or are taking antiretroviral medication
- •Be pregnant or nursing. Females must provide negative pregnancy urine tests upon hospital admission and at the end of study participation. Females must either be unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device, condoms, or spermicide)
- •Have asthma or currently use theophylline or other sympathomimetics
- •Be taking a medication that potently inhibits CYP 3A4, as this enzyme metabolizes the study medications. Potent inhibitors include clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole
- •Have any other illness, condition, or use of psychotropic medications, which in the opinion of the PI and/or the admitting physician would preclude safe and/or successful completion of the study
研究组 & 干预措施
placebo
placebo po 1x/day from day -12 through 4
干预措施: Doxazosin (Drug)
placebo
placebo po 1x/day from day -12 through 4
干预措施: Modafinil (Drug)
placebo
placebo po 1x/day from day -12 through 4
干预措施: cocaine (Drug)
placebo
placebo po 1x/day from day -12 through 4
干预措施: Placebo (Drug)
doxazosin 8 mg
day -12 through -9: Doxazosin 1 mg po 1x/day day -8 through -5: Doxazosin 2 mg po 1x/day day -4 through -1: Doxazosin 4 mg po 1x/day day 1 through 4: Doxazosin 8 mg po 1x/day
干预措施: Doxazosin (Drug)
doxazosin 8 mg
day -12 through -9: Doxazosin 1 mg po 1x/day day -8 through -5: Doxazosin 2 mg po 1x/day day -4 through -1: Doxazosin 4 mg po 1x/day day 1 through 4: Doxazosin 8 mg po 1x/day
干预措施: Modafinil (Drug)
doxazosin 8 mg
day -12 through -9: Doxazosin 1 mg po 1x/day day -8 through -5: Doxazosin 2 mg po 1x/day day -4 through -1: Doxazosin 4 mg po 1x/day day 1 through 4: Doxazosin 8 mg po 1x/day
干预措施: cocaine (Drug)
doxazosin 8 mg
day -12 through -9: Doxazosin 1 mg po 1x/day day -8 through -5: Doxazosin 2 mg po 1x/day day -4 through -1: Doxazosin 4 mg po 1x/day day 1 through 4: Doxazosin 8 mg po 1x/day
干预措施: Placebo (Drug)
结局指标
主要结局
Subjective effects (VAS) - change from baseline over 60 minutes
时间窗: baseline-post cocaine (5, 15, 30, 45, and 60 minutes following each infusion)
difference between the peak "High" VAS rating observed post-cocaine infusion and that observed at baseline prior to the infusion
次要结局
- heart rate change from baseline over 60 minutes(baseline-post cocaine (continuous first 30 minutes post cocaine session and 45 and 60 min post cocaine))
- blood pressure change from baseline over 60 minutes(baseline-post cocaine (continuous first 30 minutes post cocaine session and 45 and 60 min post cocaine))
研究者
Christopher Verrico
Associate Professor, Psychiatry Research
Baylor College of Medicine