Study of Dexmedetomidine for the Reversal of Cocaine's Effects on Myocardial Perfusion
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 1
- 主要终点
- Myocardial Perfusion
研究概览
简要总结
This study will use myocardial contrast echocardiography performed during a continuous intravenous infusion of Definity microbubbles (Perflutren lipid microbubbles) to determine if dexmedetomidine (an intravenous central sympatholytic drug) can reverse all the cardiovascular effects of low-dose intranasal cocaine-including vasoconstriction in the coronary microcirculation-both in cocaine-naïve and non-treatment seeking cocaine-addicted subjects.
详细描述
Each subject will be participating in three study visits: Screening Visit, Visit 1: a low-dose dobutamine visit and Visit 2: a low-dose cocaine visit. At the dobutamine visit, the subject will only receive low-dose dobutamine, which will be used as an internal inotropic/vasodilator control for cocaine. At the cocaine visit, the subject will receive low-dose intranasal cocaine followed by either the active study drug (dexmedetomidine) or an inactive placebo (saline). Both cocaine and dobutamine will increase myocardial contractility and oxygen demand, thereby stimulating metabolic vasodilation. If, as predicted, cocaine also causes α-adrenergic agonist in the coronary microcirculation, then myocardial blood flow should increase less with cocaine then with dobutamine for a given level of myocardial oxygen demand. We will study if dexmedetomidine, a central sympatholytic, can normalize this cocaine effect. We previously have used dobutamine as a comparator for cocaine in our research. At both visits, myocardial contrast echocardiography will be used to measure regional myocardial perfusion.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult subjects ages of 18-65 years without any history of substance abuse (other than tobacco), including narcotics, abuse of prescription painkillers, cocaine or any other recreational drug
排除标准
- •Known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts or detected by screening echocardiogram performed prior to I.V. infusion of Definity microbubbles
- •Hypersensitivity or prior reactions to Definity microbubbles
- •Pregnant or nursing women
- •Any evidence of cardiopulmonary disease by history or physical examination, including subjects who are taking any cardiovascular medications of any sort
- •History of hypertension or BP at time of consent > 140/90 mm Hg
- •Any history of substance abuse (other than tobacco), including narcotics, prescription painkillers, cocaine or any other recreational drug (any person that says they have EVER tried these drugs will be excluded from this study)
- •Subjects reporting alcohol intake of more than 2 drinks/day
- •Severe psychiatric illness (e.g., schizophrenia, suicidal depression) in addition to drug dependence, which may signify a high risk of addiction
- •Diabetes mellitus or any other systemic illness
- •Individuals with a history of pseudocholinesterase deficiency
- •Hypersensitivity to dexmedetomidine or lorazepam
- •The presence of alcohol by breathalyzer
- •Subjects who have poor echocardiography images will be screen failed.
- •Persons with mechanically, magnetically, or electrically activated implants, such as cardiac pacemakers, neurostimulators, and infusion pumps (MRI only).
- •Persons with ferromagnetic implants and ferromagnetic foreign bodies, such as intracranial, aneurysm clips, shrapnel and intraocular metal chips as these could become dislodged (MRI only).
- •Persons unable to tolerate MRI imaging secondary to an inability to lie supine or severe claustrophobia (MRI only).
- •Persons whose renal function test does not meet CSMC standard of care MRI contrast protocol requirements (GFR <45ml/min).
- •Persons with allergy to animal dander or animal-instigated asthma
- •Persons with a history of kidney or liver disease.
研究组 & 干预措施
Dexmedetomidine and intranasal cocaine
Intranasal cocaine administration (2 mg/kg) then Dexmedetomidine (0.3-0.6 mcg/kg) infusion
干预措施: Dexmedetomidine (Drug)
Dexmedetomidine and intranasal cocaine
Intranasal cocaine administration (2 mg/kg) then Dexmedetomidine (0.3-0.6 mcg/kg) infusion
干预措施: Intranasal cocaine (Drug)
Normal saline and intranasal cocaine
Intranasal cocaine administration (2 mg/kg) then Saline (over 10 minutes I.V. infusion)
干预措施: Normal Saline (Drug)
Normal saline and intranasal cocaine
Intranasal cocaine administration (2 mg/kg) then Saline (over 10 minutes I.V. infusion)
干预措施: Intranasal cocaine (Drug)
结局指标
主要结局
Myocardial Perfusion
时间窗: Baseline and Immediately after acute administration of study drug (Day 1)
Myocardial perfusion will be measured by myocardial contrast echocardiography after dexmedetomidine administration and compared to baseline. There will be no repeat dosing of dexmedetomidine. No longer term outcomes are measured.
次要结局
未报告次要终点