Intravenous Norepinephrine for Orthostatic Hypotension

NCT01285908 | Completed Phase 1 Results DMC

• 2 other identifiers: 11008511-N-0085
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Orthostatic Hypertension

Keywords

Baroreceptor; Norepinephrine; Orthostatic Hypotension; Sympathetic Nervous System; Blood Pressure

Outcome Measures

Primary Outcomes (3)

• Blood Pressure (Systolic)

  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.

  2 experimental days

• Blood Pressure (Diastolic)

  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.

  2 experimental days

• Blood Pressure (Mean)

  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.

  2 experimental days

Secondary Outcomes (6)

• 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

Study Arms (3)

Baseline

NO INTERVENTION

Baseline values measured at various tilt angles, so that each participant may serve as their own control.

Saline infusion

PLACEBO COMPARATOR

Subjects received a saline IV infusion as a placebo, while measurements were taken at various tilt angles.

Drug: Intravenous Norepinephrine Infusion

Norepinephrine Infusion

ACTIVE COMPARATOR

Subjects were given an norepinephrine infusion at various tilt angles, while measurements were taken.

Drug: Intravenous Norepinephrine Infusion

Interventions

Intravenous Norepinephrine Infusion DRUG

Norepinephrine Infusion; Saline infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Polinsky RJ, Samaras GM, Kopin IJ. Sympathetic neural prosthesis for managing orthostatic hypotension. Lancet. 1983 Apr 23;1(8330):901-4. doi: 10.1016/s0140-6736(83)91329-6.

  PMID: 6132222 BACKGROUND

• Oldenburg O, Mitchell A, Nurnberger J, Koeppen S, Erbel R, Philipp T, Kribben A. Ambulatory norepinephrine treatment of severe autonomic orthostatic hypotension. J Am Coll Cardiol. 2001 Jan;37(1):219-23. doi: 10.1016/s0735-1097(00)01062-7.

  PMID: 11153742 BACKGROUND

• Goldstein DS, Horwitz D, Keiser HR, Polinsky RJ, Kopin IJ. Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension. J Clin Invest. 1983 Nov;72(5):1748-58. doi: 10.1172/JCI111134.

  PMID: 6630523 BACKGROUND

• Goldstein DS, Sewell L, Holmes C, Pechnik S, Diedrich A, Robertson D. Temporary elimination of orthostatic hypotension by norepinephrine infusion. Clin Auton Res. 2012 Dec;22(6):303-6. doi: 10.1007/s10286-012-0176-4. Epub 2012 Sep 16.

  PMID: 22983778 BACKGROUND

MeSH Terms

Conditions

Hypotension, Orthostatic

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Dr. David S. Goldstein
• Organization: National Institute of Neurological Disorders & Stroke

david.goldstein1@nih.gov

Study Officials

• Lawrence Latour, Ph.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2011
• First Posted: January 28, 2011
• Study Start: January 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: October 10, 2014
• Results First Posted: March 26, 2014

Record last verified: 2014-09

Locations

US (1)