Autonomic Nervous System Diseases, Orthostatic Hypotension, Dopamine Beta-Hydroxylase Deficiency, Orthostatic Intolerance
Conditions
Keywords
autonomic nervous system diseases, blood pressure, congenital, orthostasis, catecholamines
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.
Interventions
PROCEDUREStanding or upright tilt
stand upright or tilt table test
PROCEDUREMicroneurography
Recording from sympathetic nerve
PROCEDUREQSweat
quantitative sweat testing
DEVICEneck cuff stimulation
Blood pressure receptors in the neck arteries may be stimulated by applying suction through a collar around the neck.
DRUGphenylephrine,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
DRUGclonidine,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
PROCEDUREBodPod
Determination of body composition
PROCEDUREEye 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)
PROCEDURESleep study
Recording of sleep pattern overnight
PROCEDUREPain response testing
Subjects will rate the quality and intensity of 2 pain tasks.
PROCEDUREMetabolic chamber
Determination of metabolic rate via 24hr stay in whole-room indirect calorimeter
PROCEDUREBrain function studies
Questionnaires and computer tasks, an EEG and an MRI may be used to assess brain function.
PROCEDUREBicycle Exercise Test
Blood pressure and heart rate may be monitored while exercising on a stationary bicycle.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| hemodynamic changes with standing | following test |
Secondary
| Measure | Time frame |
|---|---|
| Pain response | once |
| Responses on questionnaires and computer tasks designed to assess brain function | once |
| sympathetic nerve activity | during stimulation of sympathetic nervous system |
| quantitative sweat testing | 2 hours |
| Metabolic rate | once |
| blood and urine hormones | after test |
| blood volume | during supine and/or upright postures |
| Sleep efficiency | once |
| Eye function | once |
Countries
United States
Outcome results
None listed