Pharmacodynamic and Pharmacokinetic Interactions Between Intravenous Cocaine and Acetazolamide or Quinine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Pharmacokinetic changes for IV cocaine, acetazolamide, quinine
研究概览
简要总结
Background:
- Scientists are studying medications that may be useful in treating cocaine addiction. It is important in these studies to know whether study participants are always taking their medications as directed. This study will look at two chemicals to see if they can be used to determine whether participants are taking their medications as directed. Because acetazolamide and quinine can be measured in plasma and urine, they are good test subjects for this study. They will be given alone, and combined with intravenous cocaine.
Objectives:
- To see how they body handles acetazolamide and quinine alone, and when combined with cocaine.
Eligibility:
- Individuals between 18 and 50 years of age who have smoked or used IV cocaine for at least one year and at least three times per month during the three months prior to screening. Urine test positive for cocaine within the prior 6 months
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will also be collected.
- This study will involve a 12-day inpatient stay at the National Institutes of Health.
- On days 1, 5, and 10, participants will receive a dose of cocaine. Blood, urine, breath, and saliva samples will be collected up to 18 times a day for up to about 24 hours.
- On days 2, 3, 4, and 5, participants will receive acetazolamide. Regular blood samples will be collected on Day 4.
- Day 6 is a wash-out day with no drugs or blood tests.
- On days 7, 8, 9, and 10, participants will receive quinine. Regular blood samples will be collected on Day 9.
- On day 11, blood, urine, breath, and saliva samples will be collected in the early morning. Participants will be able to leave later in the day.
详细描述
Background: Cocaine dependence is a public health concern worldwide, with no FDA-approved pharmacological treatment for this condition. Thus, there is a need for controlled clinical trials to evaluate potential new pharmacological treatments. Adherence to a medication regime is a major factor in the success of treatment. In controlled clinical trials, medication adherence is often monitored by measuring specific markers ingested with the medication. No such markers are validated for use in studies of cocaine dependence treatment.
Objective: Evaluate the feasibility of oral acetazolamide and quinine as adherence markers in trials of cocaine dependence treatment by determining their pharmacodynamic and pharmacokinetic interactions with intravenous (IV) cocaine.
Study Population: Up to 30 healthy cocaine users aged 18-50 years who smoked or used IV cocaine for at least one year and at least three times per month during the three months prior to screening and had a positive urine test for cocaine within the last 6 months.
Experimental Design and Methods: Participants are admitted to a secure residential research unit on and undergo baseline assessments on Day -1, receive training on Day 0, and receive single doses of IV cocaine (25 mg) on Days 1, 5 and 10. On Days 1, 5, and 10, dried blood spot specimens are collected up to 3 times daily over 1.5 h. Single oral doses of acetazolamide (15 mg) are given on Days 2-5 and quinine (80 mg) on Days 7-10. Blood, oral fluid, and breath specimens are collected for up to 71 h, 70 h, and 22 h, respectively, after drug administration on Days 1, 4, 5, 9 and 10. Participants will wear the AutoSense device on Days 1, 3, 4, 5, 8, 9 and 10 for up to 12 hours each day. All voided urine is collected throughout the study.
Outcome measures: Primary outcome measures include cocaine, benzoylecgonine, ecgonine methylester, norcocaine, acetazolamide, and quinine pharmacokinetics in plasma and urine and whether subjective and cardiovascular responses to IV cocaine are changed when coadministered with oral acetazolamide or quinine. Secondary outcome measures include cocaine pharmacokinetics in oral fluid and breath, plasma activity of BChE and carboxylesterase (enzymes which metabolize cocaine), and basal and post-cocaine administration serum concentrations of leptin and other appetitive peptides (e.g. ghrelin, GLP-1, insulin, PYY, amylin).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •INCLUSION CRITERIA
- •Age 18-50 years old
- •Smoked or used IV cocaine for at least six months and at least three times per month during the three months prior to screening. Urine test positive for cocaine within the prior 6 months
- •Adequate venous access for catheter placement
- •Serum sodium and potassium concentrations within normal limits (based on Johns Hopkins Bayview Medical Center clinical laboratory)
- •Women with reproductive potential must use a medically acceptable form of contraception for the duration of the study. Medically acceptable forms of contraception include: oral contraceptive, intrauterine device (IUD), depot hormonal preparation (ring, injection implant), or a barrier method of contraception such as a diaphragm, sponge with spermicide, or a condom.
排除标准
- •Current physical dependence on any drug other than cocaine, caffeine, or nicotine
- •Current clinically significant medical or psychiatric disorder, such as heart disease, kidney disease, liver disease, adrenal insufficiency, myasthenia gravis, glucose-6-phosphate dehydrogenase deficiency, epilepsy, stroke, optic neuritis, hyperthyroidism, glaucoma; or psychosis, panic attacks, depression, or mania
- •Current sulfa allergy
- •Currently seeking treatment for a cocaine use disorder or in such treatment within the prior 3 months
- •Current hypertension or blood pressure readings consistently above 140 mm Hg systolic or 90 mmHg diastolic while at rest
- •Heart rate consistently above 90 bpm or below 50 bpm while at rest
- •History of premature coronary artery disease or heart attack before age 50 in a first degree biological relative
- •QTc greater than 450 ms or evidence of heart block, ischemia, or other clinically significant cardiovascular disease on a 12-lead resting ECG with three-minute rhythm strip
- •Hemoglobin less than 12.5 g/dL
- •Blood donation within 8 weeks of study entry
- •History of clinically significant adverse reaction to ingestion of cocaine, acetazolamide, or quinine
- •Hypersensitivity to acetazolamide, sulfonamides, sulfonamide derivatives, quinine, mefloquine or quinidine
- •Women who are pregnant or nursing
- •Currently on anti-hypertensive medication
结局指标
主要结局
Pharmacokinetic changes for IV cocaine, acetazolamide, quinine
时间窗: 24 hours
Heart rate, blood pressure
时间窗: 3 hours
Subjective response to IV cocaine
时间窗: 3 hours
次要结局
- Esterase activity in plasma(4 days)
- Pharmacokinetic parameters for IV cocain in oral fluid(24 hours)
- Window of dectection for cocaine in oral fluid and exhaled breath(24 hours)