The Pathophysiology of Orthostatic Hypotension

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.

Conditions

• Autonomic Nervous System Diseases
• Orthostatic Hypotension
• Dopamine Beta-Hydroxylase Deficiency
• Orthostatic Intolerance

Interventions

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: 1. 0.5% proparacaine (Alcaine, Allergan, Inc) 2. Fluress (0.4% benoxinate hydrochloride, fluorescein sodium, Akorn, Inc) 3. 0.5%, 1% tropicamide (Mydriacyl, Alcon) 4. Over-the-counter preservative-free artificial tears 5. 0.25%, 2.5% and 10% phenylephrine (Bausch and Lomb) 6. 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center

  lead OTHER

Principal Investigators

• Emily M Garland, PhD · Vanderbilt University

Study Design

Allocation

NA

Purpose

SCREENING

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

12 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

1996-12-31

Primary Completion

2020-12-31

Completion

2020-12-31

Countries

• United States

Study Locations