Phase 2 N=6 Randomized Treatment

Intravenous Norepinephrine for Orthostatic Hypotension

Orthostatic Hypertension

Bottom Line

View on ClinicalTrials.gov: NCT01285908 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Mar 2014

Primary outcome: Primary: Blood Pressure (Systolic) — 156; 158; 179; 148 mm Hg

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Intravenous Norepinephrine Infusion (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
Primary completion: Sep 2012

Outcome Measures

Outcome	Result	p-value
PRIMARY Blood Pressure (Systolic)	156; 158; 179; 148; 149; 173	—
PRIMARY Blood Pressure (Diastolic)	83; 83; 95; 85; 84; 95	—
PRIMARY Blood Pressure (Mean)	107; 108; 123; 106; 106; 121	—
SECONDARY Heart Rate	62; 55; 58; 57; 56; 60	—
SECONDARY Cardiac Stroke Volume	76; 66; 83; 70; 62; 82	—
SECONDARY Cardiac Output	4.6; 3.8; 4.9; 3.9; 3.5; 5.1	—
SECONDARY Total Peripheral Resistance	22.4; 34; 27; 26.9; 33; 26	—
SECONDARY Arterial Plasma Levels of Norepinephrine	0.78; 0.82; 0.73; 0.89; 0.65; 1.99	—
SECONDARY Arterial Plasma Levels of Dihydroxyphenylglycol (DHPG)	3.42; 4.01; 4.07; 3.44; 3.97; 4.05	—

Summary

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.

Eligibility Criteria

INCLUSION CRITERIA:

A candidate subject is eligible for inclusion if he or she satisfies all of the following criteria:

Aged 18 years or over.

A confirmed diagnosis of neurogenic orthostatic hypotension related to Parkinson disease or pure autonomic failure.

Able to provide informed consent

EXCLUSION CRITERIA

A candidate subject is ineligible for inclusion if he or she satisfies any of the following criteria:

Receiving medications expected to augment or attenuate blood pressure responses to i.v. norepinephrine (such as tricyclic antidepressants or alpha-adrenoceptor blockers).

Has heart block (unless a functioning cardiac pacemaker is in place or the patient is cleared by a cardiologist).

Raynaud's phenomenon or other findings in the medical history suggest a tendency to vasospasm.

History of myocardial infarction or current evidence of symptomatic congestive heart failure or symptomatic coronary ischemia.

Current evidence of ventricular arrhythmias or frequent premature ventricular contractions.

Renal failure.

History of mesenteric ischemia.

History of cerebrovascular ischemic disease, unless corrected (e.g., by stent).

Technical or medicinal limitations that obviate safe placement of arm intravenous and intra-arterial catheters for drug infusion and blood drawing. Examples of medicinal limitations are required daily aspirin ingestion and previously documented lidocaine allergy.

Pregnant or lactating or a female of child bearing potential who refuses to have a blood test for pregnancy. (Urine pregnancy tests can yield false-negative results, due to incorrect test preparation, urine that is too dilute, or interference by several medications. We have experience with the NIH Clinical Pathology Department not calling a urine test for pregnancy positive or negative because the urine was dilute. Serum pregnancy tests do not have these limitations.)

Unable to tolerate lying supine on a tilt table.

Closed angle glaucoma.

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Data sourced from ClinicalTrials.gov (NCT01285908). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.