Autonomic Nervous System DiseasesPhase 2/3NCT00581477

Treatment of Orthostatic Hypotension

A Phase 2/3 study testing Droxidopa Oral Product in people with Autonomic Nervous System Diseases and Orthostatic Hypotension, run by Vanderbilt University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Autonomic Nervous System Diseases, Orthostatic Hypotension, Dopamine Beta-Hydroxylase Deficiency
What is being tested?: Droxidopa Oral Product
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteUnited States
Study dates: Jan 2004to Dec 2020
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

patients with severe orthostatic hypotension and other autonomic symptoms who do not meet criteria for one of our standard diagnoses
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 (cardiac, pulmonary, endocrine, gastrointestinal, rheumatologic)
anemia (Hct < 30)
women of childbearing age who are pregnant or nursing
smokers

Trial locations and contacts

1 site in 1 country.

United States1 site

Vanderbilt University
Nashville, Tennessee, 37232

Other trials in United States

About this study

Official title: Treatment of Hypotensive Patients Having a Unique Pattern of Autonomic Symptoms

The purpose of this study is to try different medications in patients with low blood pressure and other problems with their involuntary (autonomic) nervous system. The pharmacological trials in this study will perhaps lead to more effective treatment. The protocol includes single dose trials, dose-selection trials, 5-day trials and chronic (approximately 2 months) trials, although only dose-selection trials were consistently performed and have results presented.

Read the detailed description

We see many patients at the Autonomic Dysfunction Center who can be given a fairly definitive diagnosis, e.g., Orthostatic Intolerance, Pure Autonomic Failure, Multiple System Atrophy, and Baroreflex Failure. However, some patients present with a unique constellation of symptoms of autonomic dysfunction so that they do not fit into a diagnostic category. We hypothesize that a genetic cause exists in some of these patients. We further propose that our comprehensive evaluation of these patients will provide us with information on the pathophysiology of their condition and assist us in optimizing their treatment.

Conditions: Autonomic Nervous System Diseases, Orthostatic Hypotension, Dopamine Beta-Hydroxylase Deficiency, Orthostatic Intolerance
Being tested: Droxidopa Oral Product
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.

Droxidopa Oral ProductDrug
Also called L-DOPS
Droxidopa administered in increasing dosages up to 300 mg

Study groups in NCT00581477
Study group	Role	What they receive
Droxidopa	Experimental	Patients with known or suspected Dopamine beta-Hydroxylase Deficiency were administered Droxidopa doses of 25 mg, 50 mg, 100 mg, 200 mg, 250 mg or 300 mg up to three times daily. Supine and upright blood pressures were subsequently measured 60 to 240 minutes post-dose. Receives: Drug: Droxidopa Oral Product

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Systolic Blood Pressure With Standing
The difference between upright and supine systolic blood pressures (dSBP; upright - supine) was calculated for each patient at 60-240 minutes after each dose of droxidopa. For each post-dose timepoint and study day, the average of up to three blood pressure readings per droxidopa dose was calculated. Dosing is individualized for each patient based upon how well the drug is tolerated and the degree of improvement in orthostatic vital signs and symptoms following drug administration. The dosages administered, as well as the number of timepoints and days, therefore, varied between patients.
Measured: Up to 240 minutes post dose on Study Days 1, 2, 3 and 4.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2004Dec 2020

First posted27 Dec 2007 (estimated)
Study startJan 2004
Primary completionDec 2020
Study completionDec 2020

Why it stopped: 1\. enrollment slower than anticipated; 2. FDA approval of droxidopa so no longer need to treat patients on research basis; 3. personnel who were primarily responsible for the study are no longer at Vanderbilt.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Autonomic Nervous System DiseasesStudies of the same condition, open and under way.
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 2/3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Although the study was designed as a potential trial of multiple medications, plus placebo, in actuality it served as a means of safely determining the optimal dose of Droxidopa for our patients with Dopamine beta-Hydroxylase Deficiency to take at home. Before each dose of Droxidopa, blood pressure and heart rate were measured for 30 minutes. At 60 or 120 minutes after dosing, blood pressure was also measured after 5 minutes of lying down and 5 minutes of sitting or standing. These measurements were used to calculate the orthostatic change in systolic blood pressure, the primary outcome.
Masking: None (open label)
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00581477
Sponsor's protocol ID: 030750
Other IDs: P01HL056693
Status last verified: Feb 2022
First submitted: 22 Dec 2007
Last updated: 2 Mar 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Autonomic Nervous System Diseases trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Treatment of Hypotensive Patients Having a Unique Pattern of Autonomic Symptoms
ClinicalTrials.gov ID: NCT00581477
Acronym / sponsor ID: 030750
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 2/3
Study type: Interventional
Recruitment status: TerminatedReason stopped: 1\. enrollment slower than anticipated; 2. FDA approval of droxidopa so no longer need to treat patients on research basis; 3. personnel who were primarily responsible for the study are no longer at Vanderbilt.
Enrolment: 8 participants (actual)
Lead sponsor: Vanderbilt UniversityUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: Jan 2004
Primary completion: Dec 2020 (actual)
Study completion: Dec 2020 (actual)
First posted: 27 Dec 2007 (estimated)
Results: Posted 2 Mar 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Although the study was designed as a potential trial of multiple medications, plus placebo, in actuality it served as a means of safely determining the optimal dose of Droxidopa for our patients with Dopamine beta-Hydroxylase Deficiency to take at home. Before each dose of Droxidopa, blood pressure and heart rate were measured for 30 minutes. At 60 or 120 minutes after dosing, blood pressure was also measured after 5 minutes of lying down and 5 minutes of sitting or standing. These measurements were used to calculate the orthostatic change in systolic blood pressure, the primary outcome.

Arm	Type	Receives
Droxidopa	Experimental	Drug: Droxidopa Oral ProductPatients with known or suspected Dopamine beta-Hydroxylase Deficiency were administered Droxidopa doses of 25 mg, 50 mg, 100 mg, 200 mg, 250 mg or 300 mg up to three times daily. Supine and upright blood pressures were subsequently measured 60 to 240 minutes post-dose.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

patients with severe orthostatic hypotension and other autonomic symptoms who do not meet criteria for one of our standard diagnoses
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 (cardiac, pulmonary, endocrine, gastrointestinal, rheumatologic)
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
Droxidopa Oral ProductAlso: L-DOPSDroxidopa administered in increasing dosages up to 300 mg	Drug	Droxidopa

Primary outcome

Change in Systolic Blood Pressure With Standing
Time frame: Up to 240 minutes post dose on Study Days 1, 2, 3 and 4.
The difference between upright and supine systolic blood pressures (dSBP; upright - supine) was calculated for each patient at 60-240 minutes after each dose of droxidopa. For each post-dose timepoint and study day, the average of up to three blood pressure readings per droxidopa dose was calculated. Dosing is individualized for each patient based upon how well the drug is tolerated and the degree of improvement in orthostatic vital signs and symptoms following drug administration. The dosages administered, as well as the number of timepoints and days, therefore, varied between patients.

Results and safety

Results posted to the registry on 2 Mar 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Patients With Dopamine Beta-Hydroxylase Deficiency	8	6

Primary outcome: Change in Systolic Blood Pressure With Standing

Time frame: Up to 240 minutes post dose on Study Days 1, 2, 3 and 4.. Median (Inter-Quartile Range). Unit: millimeters of mercury

Measure	Droxidopa 25 mg n = 5	Droxidopa 50 mg n = 5	Droxidopa 100 mg n = 4	Droxidopa 200 mg n = 5	Droxidopa 250 mg n = 2	Droxidopa 300 mg n = 1
60 minutes post-dose (Day 1) dSBP	-47	-39	–	–	–	-21
120 minutes post-dose (Day 1) dSBP	-39.5 (-47.5 to -33)	-35.5 (-62.2 to -10.2)	-24	-31	–	–
180 minutes post-dose (Day 1) dSBP	-38	-4	–	–	–	–
240 minutes post-dose (Day 1) dSBP	-47	-7	–	–	–	–
60 minutes post-dose (Day 2) dSBP	–	–	-48 (-51 to -43)	–	–	-30
120 minutes post-dose (Day 2) dSBP	–	–	-43.5 (-65.7 to -18.8)	–	–	-13
60 minutes post-dose (Day 3) dSBP	–	–	–	-51 (-60 to -21)	–	–
120 minutes post-dose (Day 3) dSBP	–	–	–	-36.5 (-50.2 to -24.8)	–	-23

Population analysed: Data is missing for 2 participants who had previously been treated with Droxidopa. In addition, since dosing was individualized for each patient, only those participants with data available at the specified timepoint were analyzed.

Adverse events

Time frame: Patients stood for upright blood pressure measurements at 60 - 240 minutes following each dose of droxidopa and were asked about adverse events during this time period. Additionally, since patients were inpatient during the study, they were able to report any adverse events throughout the study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Droxidopa 25 mg	0 of 8 (0%)	0 of 8 (0%)	0 of 8
Droxidopa 50 mg	0 of 8 (0%)	0 of 8 (0%)	0 of 8
Droxidopa 100 mg	0 of 8 (0%)	0 of 8 (0%)	0 of 8
Droxidopa 200 mg	0 of 8 (0%)	0 of 8 (0%)	0 of 8
Droxidopa 250 mg	0 of 8 (0%)	0 of 8 (0%)	0 of 8
Droxidopa 300 mg	0 of 8 (0%)	0 of 8 (0%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

David Robertson, MD 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 2/3 study testing Droxidopa Oral Product in people with Autonomic Nervous System Diseases and Orthostatic Hypotension, run by Vanderbilt University 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: stopped early, as of the sponsor's last update on 2 Mar 2022. 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change in Systolic Blood Pressure With Standing (time frame: Up to 240 minutes post dose on Study Days 1, 2, 3 and 4.). 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 NCT00581477.

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 2 Mar 2022.