The Pathophysiology of Orthostatic Hypotension

NCT00748059 | Completed Phase 1

• 2 other identifiers: 030752HL056693
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

autonomic nervous system diseases; blood pressure; congenital; orthostasis; catecholamines

Outcome Measures

Primary Outcomes (1)

• hemodynamic changes with standing

  following test

Secondary Outcomes (9)

• 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

Study Arms (1)

A

EXPERIMENTAL

Patients with Orthostatic Hypotension

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

Interventions

Standing or upright tilt PROCEDURE

stand upright or tilt table test

A

Microneurography PROCEDURE

Recording from sympathetic nerve

A

QSweat PROCEDURE

quantitative sweat testing

A

neck cuff stimulation DEVICE

Blood pressure receptors in the neck arteries may be stimulated by applying suction through a collar around the neck.

A

phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramine DRUG

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

A

clonidine,yohimbine,metoclopramide,alpha-methyldopa DRUG

Oral Pharmacological Testing clonidine 0.1-0.3 mg, yohimbine 5-10 mg, metoclopramide 10 mg, alpha-methyldopa 62.5 mg, placebo

A

BodPod PROCEDURE

Determination of body composition

A

Eye exam PROCEDURE

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)

A

Sleep study PROCEDURE

Recording of sleep pattern overnight

A

Pain response testing PROCEDURE

Subjects will rate the quality and intensity of 2 pain tasks.

A

Metabolic chamber PROCEDURE

Determination of metabolic rate via 24hr stay in whole-room indirect calorimeter

A

Brain function studies PROCEDURE

Questionnaires and computer tasks, an EEG and an MRI may be used to assess brain function.

A

Bicycle Exercise Test PROCEDURE

Blood pressure and heart rate may be monitored while exercising on a stationary bicycle.

A

Eligibility Criteria

• Age: 12 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• medications affecting the autonomic nervous system
• any chronic illness
• anemia (Hct\<30)
• women of childbearing age who are pregnant or nursing
• smokers

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Arnold AC, Garland EM, Celedonio JE, Raj SR, Abumrad NN, Biaggioni I, Robertson D, Luther JM, Shibao CA. Hyperinsulinemia and Insulin Resistance in Dopamine beta-Hydroxylase Deficiency. J Clin Endocrinol Metab. 2017 Jan 1;102(1):10-14. doi: 10.1210/jc.2016-3274.

  PMID: 27778639 DERIVED

MeSH Terms

Conditions

Autonomic Nervous System Diseases; Hypotension, Orthostatic; dopamine beta hydroxylase deficiency; Orthostatic Intolerance; Dizziness

Interventions

Standing Position; Phenylephrine; Clonidine

Condition Hierarchy (Ancestors)

Nervous System Diseases; Primary Dysautonomias; Hypotension; Vascular Diseases; Cardiovascular Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Sensation Disorders

Intervention Hierarchy (Ancestors)

Posture; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Emily M Garland, PhD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate Professor

Study Record Dates

• First Submitted: September 5, 2008
• First Posted: September 8, 2008
• Study Start: December 1, 1996
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: May 12, 2021

Record last verified: 2021-05

Locations

US (1)