The Pathophysiology of Orthostatic Hypotension

Study Overview
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Brief Summary
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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.

Official Title
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The Pathophysiology of Orthostatic Hypotension

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

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Patients with Orthostatic Hypotension | Procedure: Standing or upright tilt<br>* stand upright or tilt table test<br>Procedure: Microneurography<br>* Recording from sympathetic nerve<br>Procedure: QSweat<br>* quantitative sweat testing<br>Device: neck cuff stimulation<br>* Blood pressure receptors in the neck arteries may be stimulated by applying suction through a collar around the neck.<br>Drug: phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramine<br>* 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<br>Drug: clonidine,yohimbine,metoclopramide,alpha-methyldopa<br>* Oral Pharmacological Testing clonidine 0.1-0.3 mg, yohimbine 5-10 mg, metoclopramide 10 mg, alpha-methyldopa 62.5 mg, placebo<br>Procedure: BodPod<br>* Determination of body composition<br>Procedure: Eye exam<br>* 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)<br>Procedure: Sleep study<br>* Recording of sleep pattern overnight<br>Procedure: Pain response testing<br>* Subjects will rate the quality and intensity of 2 pain tasks.<br>Procedure: Metabolic chamber<br>* Determination of metabolic rate via 24hr stay in whole-room indirect calorimeter<br>Procedure: Brain function studies<br>* Questionnaires and computer tasks, an EEG and an MRI may be used to assess brain function.<br>Procedure: Bicycle Exercise Test<br>* Blood pressure and heart rate may be monitored while exercising on a stationary bicycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hemodynamic changes with standing |  | following test | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autonomic nervous system diseases, blood pressure, congenital, orthostasis, catecholamines