The Pathophysiology of Orthostatic Hypotension - Full Text View

Sponsor:	Vanderbilt University
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00748059

Purpose

The purpose of this study is to determine the cause of low blood pressure in selective patients who have problems with their involuntary (autonomic) nervous system. These patients frequently have had symptoms throughout their life, and their disorder might have a genetic basis. The biochemical, physiological and pharmacological procedures in this study should help us define the problem and perhaps lead to more effective treatment.

Condition	Intervention
Autonomic Nervous System Diseases Orthostatic Hypotension	Procedure: Standing or upright tilt Procedure: Microneurography Procedure: QSweat Device: neck cuff stimulation Drug: phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramine Drug: clonidine,yohimbine,metoclopramide,alpha-methyldopa Procedure: BodPod Procedure: Eye exam Procedure: Sleep study Procedure: Pain response testing Procedure: Metabolic chamber Procedure: Brain function studies Procedure: Bicycle Exercise Test

Condition

Intervention

Autonomic Nervous System Diseases
Orthostatic Hypotension

Procedure: Standing or upright tilt
Procedure: Microneurography
Procedure: QSweat
Device: neck cuff stimulation
Drug: phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramine
Drug: clonidine,yohimbine,metoclopramide,alpha-methyldopa
Procedure: BodPod
Procedure: Eye exam
Procedure: Sleep study
Procedure: Pain response testing
Procedure: Metabolic chamber
Procedure: Brain function studies
Procedure: Bicycle Exercise Test

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Screening
Official Title:	The Pathophysiology of Orthostatic Hypotension

Resource links provided by NLM:

MedlinePlus related topics: Autonomic Nervous System Disorders Low Blood Pressure Neurologic Diseases Sweat

Drug Information available for: Isoproterenol hydrochloride Atropine Phenylephrine Phenylephrine hydrochloride Edrophonium chloride Isoproterenol sulfate Propranolol hydrochloride Metoclopramide Methyldopa Oxymetazoline Oxymetazoline hydrochloride Methyldopate hydrochloride Clonidine Clonidine hydrochloride Atropine sulfate Metoclopramide hydrochloride Sodium nitroprusside Nitroprusside

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

hemodynamic changes with standing [ Time Frame: following test ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

blood and urine hormones [ Time Frame: after test ] [ Designated as safety issue: No ]
blood volume [ Time Frame: during supine and/or upright postures ] [ Designated as safety issue: No ]
sympathetic nerve activity [ Time Frame: during stimulation of sympathetic nervous system ] [ Designated as safety issue: No ]
quantitative sweat testing [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
Eye function [ Time Frame: once ] [ Designated as safety issue: No ]
Sleep efficiency [ Time Frame: once ] [ Designated as safety issue: No ]
Metabolic rate [ Time Frame: once ] [ Designated as safety issue: No ]
Pain response [ Time Frame: once ] [ Designated as safety issue: No ]
Responses on questionnaires and computer tasks designed to assess brain function [ Time Frame: once ] [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	December 1996
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A Patients with Orthostatic Hypotension	Procedure: Standing or upright tilt stand upright or tilt table test Procedure: Microneurography Recording from sympathetic nerve Procedure: QSweat quantitative sweat testing Device: neck cuff stimulation Blood pressure receptors in the neck arteries may be stimulated by applying suction through a collar around the neck. Drug: phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramine IV Pharmacological Testing phenylephrine 12.5 - 400 ug, isoproterenol 0.1 - 0.4 ug or higher until desired effect, nitroprusside 0.1 - 1.6 ug/kg, propranolol 1.1 mg/min, edrophonium maximum of 10 mg, atropine .01 mg/kg, tyramine 250-4000 ug or higher until desired effect Drug: clonidine,yohimbine,metoclopramide,alpha-methyldopa Oral Pharmacological Testing clonidine 0.1-0.3 mg, yohimbine 5-10 mg, metoclopramide 10 mg, alpha-methyldopa 62.5 mg, placebo Procedure: BodPod Determination of body composition Procedure: Eye exam Examination of pressure in the eye and eyelid fatiguability. The following eyedrops might be used: 0.5% proparacaine (Alcaine, Allergan, Inc) Fluress (0.4% benoxinate hydrochloride, fluorescein sodium, Akorn, Inc) 0.5%, 1% tropicamide (Mydriacyl, Alcon) Over-the-counter preservative-free artificial tears 0.25%, 2.5% and 10% phenylephrine (Bausch and Lomb) 1% cyclopentolate hydrochloride (Alcon) Procedure: Sleep study Recording of sleep pattern overnight Procedure: Pain response testing Subjects will rate the quality and intensity of 2 pain tasks. Procedure: Metabolic chamber Determination of metabolic rate via 24hr stay in whole-room indirect calorimeter Procedure: Brain function studies Questionnaires and computer tasks, an EEG and an MRI may be used to assess brain function. Procedure: Bicycle Exercise Test Blood pressure and heart rate may be monitored while exercising on a stationary bicycle.

Arms

Assigned Interventions

Experimental: A

Patients with Orthostatic Hypotension

Procedure: Standing or upright tilt

stand upright or tilt table test

Procedure: Microneurography

Recording from sympathetic nerve

Procedure: QSweat

quantitative sweat testing

Device: neck cuff stimulation

Blood pressure receptors in the neck arteries may be stimulated by applying suction through a collar around the neck.

Drug: phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramine

IV Pharmacological Testing

phenylephrine 12.5 - 400 ug, isoproterenol 0.1 - 0.4 ug or higher until desired effect, nitroprusside 0.1 - 1.6 ug/kg, propranolol 1.1 mg/min, edrophonium maximum of 10 mg, atropine .01 mg/kg, tyramine 250-4000 ug or higher until desired effect

Drug: clonidine,yohimbine,metoclopramide,alpha-methyldopa

Oral Pharmacological Testing

clonidine 0.1-0.3 mg, yohimbine 5-10 mg, metoclopramide 10 mg, alpha-methyldopa 62.5 mg, placebo

Procedure: BodPod

Determination of body composition

Procedure: Eye exam

Examination of pressure in the eye and eyelid fatiguability. The following eyedrops might be used:

0.5% proparacaine (Alcaine, Allergan, Inc)
Fluress (0.4% benoxinate hydrochloride, fluorescein sodium, Akorn, Inc)
0.5%, 1% tropicamide (Mydriacyl, Alcon)
Over-the-counter preservative-free artificial tears
0.25%, 2.5% and 10% phenylephrine (Bausch and Lomb)
1% cyclopentolate hydrochloride (Alcon)

Procedure: Sleep study

Recording of sleep pattern overnight

Procedure: Pain response testing

Subjects will rate the quality and intensity of 2 pain tasks.

Procedure: Metabolic chamber

Determination of metabolic rate via 24hr stay in whole-room indirect calorimeter

Procedure: Brain function studies

Questionnaires and computer tasks, an EEG and an MRI may be used to assess brain function.

Procedure: Bicycle Exercise Test

Blood pressure and heart rate may be monitored while exercising on a stationary bicycle.

Eligibility

Ages Eligible for Study:	12 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

severe orthostatic hypotension and other autonomic symptoms but do not meet criteria for standard diagnosis
non-smokers
drug-free
able to give informed consent
free of pulmonary, renal, hematopoietic, hepatic and cardiac disease

Exclusion Criteria:

medications affecting the autonomic nervous system
any chronic illness
anemia (Hct<30)
women of childbearing age who are pregnant or nursing
smokers

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00748059

Locations

United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University

Investigators

Principal Investigator:	David Robertson, MD	Vanderbilt University
Study Director:	Emily M Garland, PhD	Vanderbilt University

More Information

Additional Information:

Autonomic Dysfunction Center Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	David Robertson, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00748059 History of Changes
Other Study ID Numbers:	030752, HL056693
Study First Received:	September 5, 2008
Last Updated:	June 28, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Vanderbilt University:

autonomic nervous system diseases
blood pressure
congenital
orthostasis
catecholamines

Additional relevant MeSH terms:

Autonomic Nervous System Diseases
Primary Dysautonomias
Hypotension
Hypotension, Orthostatic
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Atropine
Propranolol
Isoproterenol
Yohimbine
Phenylephrine
Clonidine
Methyldopa

Metoclopramide
Oxymetazoline
Tyramine
Nitroprusside
Edrophonium
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Arrhythmia Agents
Cardiovascular Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 24, 2012