Autonomic Nervous System DiseasesPhase 1NCT00748059
The Pathophysiology of Orthostatic Hypotension
A Phase 1 study testing Standing or upright tilt, Microneurography and QSweat in people with Autonomic Nervous System Diseases and Orthostatic Hypotension, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 70 years
- Conditions the study is for
- Autonomic Nervous System Diseases, Orthostatic Hypotension, Dopamine Beta-Hydroxylase Deficiency
- What is being tested?
- Standing or upright tilt, Microneurography and QSweat
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 1996to Dec 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- medications affecting the autonomic nervous system
- any chronic illness
- anemia (Hct<30)
- women of childbearing age who are pregnant or nursing
- smokers
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- Standing or upright tilt, Microneurography, QSweat, neck cuff stimulation, phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramine
- Keywords
- autonomic nervous system diseases, blood pressure, congenital, orthostasis, catecholamines
- Medical subject headings
- Autonomic Nervous System Diseases, Hypotension, Orthostatic, dopamine beta hydroxylase deficiency, Orthostatic Intolerance, Dizziness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standing or upright tiltProcedure or surgery
stand upright or tilt table test
MicroneurographyProcedure or surgery
Recording from sympathetic nerve
QSweatProcedure or surgery
quantitative sweat testing
neck cuff stimulationDevice
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,tyramineDrug
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-methyldopaDrug
Oral Pharmacological Testing
clonidine 0.1-0.3 mg, yohimbine 5-10 mg, metoclopramide 10 mg, alpha-methyldopa 62.5 mg, placebo
BodPodProcedure or surgery
Determination of body composition
Eye examProcedure or surgery
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)
Sleep studyProcedure or surgery
Recording of sleep pattern overnight
Pain response testingProcedure or surgery
Subjects will rate the quality and intensity of 2 pain tasks.
Metabolic chamberProcedure or surgery
Determination of metabolic rate via 24hr stay in whole-room indirect calorimeter
Brain function studiesProcedure or surgery
Questionnaires and computer tasks, an EEG and an MRI may be used to assess brain function.
Bicycle Exercise TestProcedure or surgery
Blood pressure and heart rate may be monitored while exercising on a stationary bicycle.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Patients with Orthostatic Hypotension Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
hemodynamic changes with standing
Measured: following test
Secondary outcomes (9)
blood and urine hormones
Measured: after test
blood volume
Measured: during supine and/or upright postures
sympathetic nerve activity
Measured: during stimulation of sympathetic nervous system
quantitative sweat testing
Measured: 2 hours
Eye function
Measured: once
Sleep efficiency
Measured: once
Metabolic rate
Measured: once
Pain response
Measured: once
Responses on questionnaires and computer tasks designed to assess brain function
Measured: once
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2008 (estimated)
- Study startDec 1996
- Primary completionDec 2020
- Study completionDec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autonomic Nervous System DiseasesStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Emily M. Garland, Vanderbilt University Medical Center
- Investigators
- Emily M Garland, PhD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00748059
- Sponsor's protocol ID
- 030752
- Other IDs
- HL056693
- Status last verified
- May 2021
- First submitted
- 5 Sep 2008
- Last updated
- 12 May 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 27778639
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Pathophysiology of Orthostatic Hypotension
- ClinicalTrials.gov ID
- NCT00748059
- Acronym / sponsor ID
- 030752
- Conditions
- Autonomic Nervous System Diseases, Orthostatic Hypotension, Dopamine Beta-Hydroxylase Deficiency, Orthostatic Intolerance
- Keywords
- autonomic nervous system diseases, blood pressure, congenital, orthostasis, catecholamines
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- Dec 1996
- Primary completion
- Dec 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 8 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | 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 TestPatients with Orthostatic Hypotension |
Who may qualify
- Ages
- 12 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- medications affecting the autonomic nervous system
- any chronic illness
- anemia (Hct<30)
- women of childbearing age who are pregnant or nursing
- smokers
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standing or upright tiltstand upright or tilt table test | Procedure or surgery | A |
| MicroneurographyRecording from sympathetic nerve | Procedure or surgery | A |
| QSweatquantitative sweat testing | Procedure or surgery | A |
| neck cuff stimulationBlood pressure receptors in the neck arteries may be stimulated by applying suction through a collar around the neck. | Device | A |
| phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramineIV 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 | A |
| clonidine,yohimbine,metoclopramide,alpha-methyldopaOral Pharmacological Testing clonidine 0.1-0.3 mg, yohimbine 5-10 mg, metoclopramide 10 mg, alpha-methyldopa 62.5 mg, placebo | Drug | A |
| BodPodDetermination of body composition | Procedure or surgery | A |
| Eye examExamination 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 or surgery | A |
| Sleep studyRecording of sleep pattern overnight | Procedure or surgery | A |
| Pain response testingSubjects will rate the quality and intensity of 2 pain tasks. | Procedure or surgery | A |
| Metabolic chamberDetermination of metabolic rate via 24hr stay in whole-room indirect calorimeter | Procedure or surgery | A |
| Brain function studiesQuestionnaires and computer tasks, an EEG and an MRI may be used to assess brain function. | Procedure or surgery | A |
| Bicycle Exercise TestBlood pressure and heart rate may be monitored while exercising on a stationary bicycle. | Procedure or surgery | A |
Primary outcome
hemodynamic changes with standing
Time frame: following test
9 secondary outcomes
blood and urine hormones
Time frame: after test
blood volume
Time frame: during supine and/or upright postures
sympathetic nerve activity
Time frame: during stimulation of sympathetic nervous system
quantitative sweat testing
Time frame: 2 hours
Eye function
Time frame: once
Sleep efficiency
Time frame: once
Metabolic rate
Time frame: once
Pain response
Time frame: once
Responses on questionnaires and computer tasks designed to assess brain function
Time frame: once
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2021.
- Derived from this study: PubMed 27778639Arnold 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emily M Garland, PhD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Standing or upright tilt, Microneurography and QSweat in people with Autonomic Nervous System Diseases and Orthostatic Hypotension, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
hemodynamic changes with standing (time frame: following test). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00748059, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2021.