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The Pathophysiology of Orthostatic Hypotension

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
David Robertson, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00748059
First received: September 5, 2008
Last updated: October 14, 2016
Last verified: October 2016
  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 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 Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Screening
Official Title: The Pathophysiology of Orthostatic Hypotension

Resource links provided by NLM:


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 2017
Estimated Primary Completion Date: December 2017 (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:

  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.

  Eligibility

Ages Eligible for Study:   12 Years to 70 Years   (Child, Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Responsible Party: David Robertson, Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00748059     History of Changes
Other Study ID Numbers: 030752  HL056693 
Study First Received: September 5, 2008
Last Updated: October 14, 2016
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:
Hypotension
Nervous System Diseases
Hypotension, Orthostatic
Autonomic Nervous System Diseases
Primary Dysautonomias
Orthostatic Intolerance
Vascular Diseases
Cardiovascular Diseases
Neurologic Manifestations
Signs and Symptoms
Yohimbine
Phenylephrine
Atropine
Tyramine
Oxymetazoline
Methyldopa
Propranolol
Clonidine
Isoproterenol
Metoclopramide
Edrophonium
Nitroprusside
Mydriatics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-2 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents

ClinicalTrials.gov processed this record on December 02, 2016