The Pathophysiology of Orthostatic Hypotension

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00748059

Collaborator

(none)

Enrollment

Location

Arm

288

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Autonomic Nervous System Diseases Orthostatic Hypotension Dopamine Beta-Hydroxylase Deficiency Orthostatic Intolerance	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	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

The Pathophysiology of Orthostatic Hypotension

Study Start Date :

Dec 1, 1996

Actual Primary Completion Date :

Dec 1, 2020

Actual Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

Outcome Measures

Primary Outcome Measures

hemodynamic changes with standing [following test]

Secondary Outcome Measures

blood and urine hormones [after test]
blood volume [during supine and/or upright postures]
sympathetic nerve activity [during stimulation of sympathetic nervous system]
quantitative sweat testing [2 hours]
Eye function [once]
Sleep efficiency [once]
Metabolic rate [once]
Pain response [once]
Responses on questionnaires and computer tasks designed to assess brain function [once]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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