The Pathophysiology of Orthostatic Hypotension

NCT ID: NCT00748059

Last Updated: 2021-05-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-12-31

Study Completion Date

2020-12-31

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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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A

Patients with Orthostatic Hypotension

Group Type EXPERIMENTAL

Standing or upright tilt

Intervention Type PROCEDURE

stand upright or tilt table test

Microneurography

Intervention Type PROCEDURE

Recording from sympathetic nerve

QSweat

Intervention Type PROCEDURE

quantitative sweat testing

neck cuff stimulation

Intervention Type DEVICE

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

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

Intervention Type 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

clonidine,yohimbine,metoclopramide,alpha-methyldopa

Intervention Type DRUG

Oral Pharmacological Testing

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

BodPod

Intervention Type PROCEDURE

Determination of body composition

Eye exam

Intervention Type 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)

Sleep study

Intervention Type PROCEDURE

Recording of sleep pattern overnight

Pain response testing

Intervention Type PROCEDURE

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

Metabolic chamber

Intervention Type PROCEDURE

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

Brain function studies

Intervention Type PROCEDURE

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

Bicycle Exercise Test

Intervention Type PROCEDURE

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

Interventions

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Standing or upright tilt

stand upright or tilt table test

Intervention Type PROCEDURE

Microneurography

Recording from sympathetic nerve

Intervention Type PROCEDURE

QSweat

quantitative sweat testing

Intervention Type PROCEDURE

neck cuff stimulation

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

Intervention Type DEVICE

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

Intervention Type 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

Intervention Type DRUG

BodPod

Determination of body composition

Intervention Type 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)

Intervention Type PROCEDURE

Sleep study

Recording of sleep pattern overnight

Intervention Type PROCEDURE

Pain response testing

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

Intervention Type PROCEDURE

Metabolic chamber

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

Intervention Type PROCEDURE

Brain function studies

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

Intervention Type PROCEDURE

Bicycle Exercise Test

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

Intervention Type PROCEDURE

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
Minimum Eligible Age

12 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vanderbilt University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Emily M. Garland

Research Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Emily M Garland, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

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Vanderbilt University

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 27778639 (View on PubMed)

Other Identifiers

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HL056693

Identifier Type: -

Identifier Source: secondary_id

030752

Identifier Type: -

Identifier Source: org_study_id

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