Safety and Efficacy of Intravenous Norepinephrine for Orthostatic Hypotension
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Blood Pressure (Mean)
研究概览
简要总结
Background:
- Orthostatic hypotension is a fall in blood pressure when standing up. Normally, a reflex action of the automatic nervous system makes blood vessels tighten when people stand up. The nervous system releases the chemical norepinephrine, which tightens blood vessels and keeps blood pressure in check. In orthostatic hypotension, the nervous system does not release enough norepinephrine when a person stands up, which can cause fainting or falling. Researchers are interested in determining whether norepinephrine given as a drug by vein can help maintain blood pressure during changes in body position.
Objectives:
- To determine whether intravenous norepinephrine can maintain blood pressure in people with orthostatic hypotension.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with orthostatic hypotension related to Parkinson's disease or pure autonomic failure.
Design:
- This study will require a 2-day inpatient admission to the NIH Clinical Center. The first day will involve laboratory evaluation and the second day will involve testing with norepinephrine. The second day requires an overnight stay.
- Participants will be screened with a medical history and physical examination, blood samples, and an electrocardiogram or echocardiogram.
- Participants who are on medications may be asked to taper or discontinue one or more medications for the purposes of this study. Participants may not take aspirin or any drugs that slow blood clotting for 7 days before study participation.
- Day 1: Participants will have a clear liquid breakfast, and will have a 1-hour baseline tilt table test to monitor blood flow, skin temperature, sweating, and blood pressure. Body temperature and breathing will also be monitored.
- Day 2: Participants will have a clear liquid breakfast, and will have a 2-hour tilt table test. Initial blood pressure readings will be taken, and an intravenous line will be placed. Participants will then receive norepinephrine or saline, followed by additional position changes of the tilt table to measure blood pressure differences before returning to the starting position. After about 10 minutes, the tilt table testing and infusion will be repeated with the other drug (saline or norepinephrine).
- Participants will be discharged 24 hours after the testing is complete.
详细描述
Objective:
Patients with chronic autonomic failure (CAF) often have disabling orthostatic hypotension (OH). In CAF, OH results from deficient baroreflex-mediated release of norepinephrine (NE) from sympathetic nerves. In patients with pure autonomic failure (PAF) or Parkinson disease (PD) with OH, cardiac and extra-cardiac noradrenergic denervation exacerbates effects of baroreflex failure. OH in CAF patients is often associated with supine hypertension, which can be severe. Drugs to treat OH worsen supine hypertension. Therefore, the combination of OH with supine hypertension poses a difficult therapeutic challenge. This protocol is a first step toward development of a prosthetic baroreceptor system to maintain blood pressure during orthostasis without worsening supine hypertension. In patients with PAF or PD+OH NE is infused i.v. at doses titrated individually to maintain blood pressure during head-up tilt at increasing angles from horizontal. Blood pressure is monitored continuously directly via an intra-arterial catheter. Because of the phenomenon of denervation supersensitivity, we anticipate that patients with OH associated with sympathetic noradrenergic denervation, as in PAF and PD, should be especially responsive to i.v. norepinephrine.
Study Population:
Patients with Parkinson disease and orthostatic hypotension or with pure autonomic failure.
Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Saline infusion
Subjects received a saline IV infusion as a placebo, while measurements were taken at various tilt angles.
干预措施: Intravenous Norepinephrine Infusion (Drug)
Norepinephrine Infusion
Subjects were given an norepinephrine infusion at various tilt angles, while measurements were taken.
干预措施: Intravenous Norepinephrine Infusion (Drug)
结局指标
主要结局
Blood Pressure (Mean)
时间窗: 2 experimental days
The extent to which norepinephrine infusion maintains average blood pressure, by comparison with the fractional changes in blood pressure at varying tilt angles during baseline and saline infusion.
Blood Pressure (Systolic)
时间窗: 2 experimental days
The extent to which norepinephrine infusion maintains blood pressure, by comparison with the changes in systolic pressure at varying tilt angles during baseline and saline infusion.
Blood Pressure (Diastolic)
时间窗: 2 experimental days
The extent to which norepinephrine infusion maintains blood pressure, by comparison with the changes in diastolic pressure at varying tilt angles during baseline and saline infusion.
次要结局
- Heart Rate(2 experimental days)
- Cardiac Stroke Volume(2 experimental days)
- Cardiac Output(2 experimental days)
- Total Peripheral Resistance(2 experimental days)
- Arterial Plasma Levels of Norepinephrine(2 experimental days)
- Arterial Plasma Levels of Dihydroxyphenylglycol (DHPG)(2 experimental days)