Intravenous Norepinephrine for Orthostatic Hypotension
|ClinicalTrials.gov Identifier: NCT01285908|
Recruitment Status : Completed
First Posted : January 28, 2011
Results First Posted : March 26, 2014
Last Update Posted : October 10, 2014
- 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.
- To determine whether intravenous norepinephrine can maintain blood pressure in people with orthostatic hypotension.
- Individuals at least 18 years of age who have been diagnosed with orthostatic hypotension related to Parkinson's disease or pure autonomic failure.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Orthostatic Hypertension||Drug: Intravenous Norepinephrine Infusion||Phase 1 Phase 2|
Hide Detailed Description
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.
Patients with Parkinson disease and orthostatic hypotension or with pure autonomic failure.
This is a placebo controlled study that consists of two experimental days per participant. On a day before the day of norepinephrine (NE) infusion, the patient undergoes head-up tilting (typically at 15, 30, 45, and 60 degrees from horizontal) while blood pressure is monitored. Tilt angles are increased until the patient has orthostatic symptoms, systolic pressure decreases to less than 90 mm Hg, or systolic pressure decreases by more than 80 mm Hg. On the day of NE infusion patients, receive NE and placebo with the sequence of treatments randomized. If the patient has severe supine hypertension (more than 200 mm Hg systolic), then NE is infused beginning with the patient at whatever tilt angle is required for baseline pressure to be less than 200 mm Hg. NE is infused at doses titrated to keep directly recorded systolic blood pressure at or above the baseline value during exposure to higher tilt angles. When placebo is given, angles of tilt are increased until the patient has orthostatic symptoms, systolic pressure decreases to less than 90 mm Hg, or systolic pressure decreases by more than 80 mm Hg.
The extent to which NE infusion can maintain blood pressure is tested by comparison of the fractional changes in systolic blood pressure at the same tilt angles during NE infusion vs. placebo infusion.
- Blood pressures (systolic, diastolic, mean)
- Symptoms of orthostatic intolerance
- Hemodynamics (e.g., total peripheral resistance)
- Arterial plasma levels of norepinephrine and related neurochemicals
Patients undergo head-up tilt at the same angles to verify orthostatic hypotension if norepinephrine is not infused.
The study is done in the NIH Clinical Center in Bethesda, MD.
The Principal Investigator is David S. Goldstein, MD PhD, Chief, Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, phone 301-496-2103, e-mail firstname.lastname@example.org. The contact for patient care coordination is Tereza Jenkins, phone 301-496-1115, e-mail email@example.com. The research contact (e.g., for database coordination) is Sandra Pechnik, phone 301-435-5166, e-mail firstname.lastname@example.org.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety and Efficacy of Intravenous Norepinephrine for Orthostatic Hypotension|
|Study Start Date :||January 2011|
|Actual Primary Completion Date :||September 2012|
|Actual Study Completion Date :||September 2012|
No Intervention: Baseline
Baseline values measured at various tilt angles, so that each participant may serve as their own control.
Placebo Comparator: Saline infusion
Subjects received a saline IV infusion as a placebo, while measurements were taken at various tilt angles.
|Drug: Intravenous Norepinephrine Infusion|
Active Comparator: Norepinephrine Infusion
Subjects were given an norepinephrine infusion at various tilt angles, while measurements were taken.
|Drug: Intravenous Norepinephrine Infusion|
- Blood Pressure (Systolic) [ Time Frame: 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) [ Time Frame: 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.
- Blood Pressure (Mean) [ Time Frame: 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.
- Heart Rate [ Time Frame: 2 experimental days ]The extent to which norepinephrine infusion affects heart rate, by comparison of beat-to-beat heart rate at varying tilt angles during baseline and saline infusion.
- Cardiac Stroke Volume [ Time Frame: 2 experimental days ]The extent to which norepinephrine infusion affects cardiac stroke volume, by comparison of cardiac stroke volume at varying tilt angles during baseline and saline infusion.
- Cardiac Output [ Time Frame: 2 experimental days ]The extent to which norepinephrine infusion affects cardiac output, by comparison of cardiac output at varying tilt angles during baseline and saline infusion.
- Total Peripheral Resistance [ Time Frame: 2 experimental days ]The extent to which norepinephrine infusion affected total peripheral resistance, by comparison of total peripheral resistance at varying tilt angles during baseline and saline infusion.
- Arterial Plasma Levels of Norepinephrine [ Time Frame: 2 experimental days ]Plasma levels of norepinephrine are obtained from blood samples via IV catheter.
- Arterial Plasma Levels of Dihydroxyphenylglycol (DHPG) [ Time Frame: 2 experimental days ]Plasma levels of dihydroxyphenylglycol are obtained from blood samples via IV catheter.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01285908
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Lawrence Latour, Ph.D.||National Institute of Neurological Disorders and Stroke (NINDS)|