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.

Study Type: Interventional

Study Design: Screening, Non-Randomized, Single Blind (Subject), Parallel Assignment

Study Primary Completion Date: December 2011

Intervention(s) in this Clinical Trial

• Procedure: Standing or upright tilt
  • stand upright or tilt table test
• Procedure: Microneurography
  • Recording from sympathetic nerve
• Procedure: QSweat
  • quantitative sweat testing
• Radiation: Daxor
  • 131-I-Human Serum Albumin Blood Volume Assessment Kit
• 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Patients with Orthostatic Hypotension

Primary Measures

• hemodynamic changes with standing
  • Time Frame: following test
    Safety Issue?: No

Secondary Measures

• blood and urine hormones
  • Time Frame: after test
    Safety Issue?: No
• blood volume
  • Time Frame: during supine and/or upright postures
    Safety Issue?: No
• sympathetic nerve activity
  • Time Frame: during stimulation of sympathetic nervous system
    Safety Issue?: No
• quantitative sweat testing
  • Time Frame: 2 hours
    Safety Issue?: No
• Eye function
  • Time Frame: once
    Safety Issue?: No
• Sleep efficiency
  • Time Frame: once
    Safety Issue?: No
• Metabolic rate
  • Time Frame: once
    Safety Issue?: No
• Pain response
  • Time Frame: once
    Safety Issue?: No
• Responses on questionnaires and computer tasks designed to assess brain function
  • Time Frame: once
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Vanderbilt University

Overall Clinical Trial Officials and Contacts

David Robertson, MD Principal Investigator Vanderbilt University  

Overall Contact: Bonnie K Black, RN 615 343 6862 adc.research@vanderbilt.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00748059

Study ID Number: 030752

ClinicalTrials.gov Identifier: NCT00748059

Health Authority: United States: Food and Drug Administration

Autonomic Dysfunction Center Website