Intravenous Norepinephrine for Orthostatic Hypotension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier:
NCT01285908
First received: January 25, 2011
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

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.

Condition Intervention Phase
Orthostatic Hypertension
Drug: Intravenous Norepinephrine Infusion
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Intravenous Norepinephrine for Orthostatic Hypotension

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Blood Pressure (Systolic) [ Time Frame: 2 experimental days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Heart Rate [ Time Frame: 2 experimental days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Plasma levels of norepinephrine are obtained from blood samples via IV catheter.

  • Arterial Plasma Levels of Dihydroxyphenylglycol (DHPG) [ Time Frame: 2 experimental days ] [ Designated as safety issue: No ]
    Plasma levels of dihydroxyphenylglycol are obtained from blood samples via IV catheter.


Enrollment: 6
Study Start Date: January 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
N/A
Active Comparator: Norepinephrine Infusion
Subjects were given an norepinephrine infuson at various tilt angles, while measurements were taken.
Drug: Intravenous Norepinephrine Infusion
N/A

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01285908

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Lawrence Latour, Ph.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT01285908     History of Changes
Other Study ID Numbers: 110085, 11-N-0085
Study First Received: January 25, 2011
Results First Received: September 24, 2013
Last Updated: February 25, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Baroreceptor
Norepinephrine
Orthostatic Hypotension
Sympathetic Nervous System
Blood Pressure

Additional relevant MeSH terms:
Hypotension
Hypotension, Orthostatic
Orthostatic Intolerance
Hypertension
Vascular Diseases
Cardiovascular Diseases
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Norepinephrine
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014