Autonomic FailurePhase 1NCT02897063
Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure
A Phase 1 study testing Droxidopa and Midodrine in people with Autonomic Failure and Pure Autonomic Failure, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to learn more about the effects of midodrine and droxidopa, two medications used for the treatment of orthostatic hypotension (low blood pressure on standing), on the veins of the abdomen of patients with autonomic failure. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Autonomic Failure, Pure Autonomic Failure, Multiple System Atrophy
- What is being tested?
- Droxidopa and Midodrine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to Oct 2026
- 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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects, age 40-80 years with possible or probable Multiple System Atrophy, Pure Autonomic Failure, or Parkinson disease, as defined by Consensus Criteria.
- Neurogenic orthostatic hypotension defined as a ≥30-mmHg decrease in systolic blood pressure within 3 minutes of standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes.
- Subjects able and willing to provide informed consent.
Who cannot join
- Supine hypertension, defined as systolic blood pressure of ≥ 160 mmHg measured on two separate occasions.
- Pregnancy.
- Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathies, and autoimmune neuropathies.
- History of known aortic aneurisms, thoracic, abdominal or pelvic surgery in the past 6 months.
- Symptomatic abdominal or inguinal hernias.
- Severe gastroesophageal reflux.
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- Recent fractures or fissures of ribs, thoracic or lumbar spine.
- Medical devices implanted on the abdominal wall or abdomen that would interfere with the abdominal compression.
- Intolerance to any increase in intraabdominal pressure.
- Clinically unstable coronary artery disease or major cardiovascular or neurological event in the past 6 months, and other factors which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing.
Trial locations and contacts
1 site in 1 country.
United States1 site
Autonomic Dysfunction Center/ Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: The Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure Aim 2 of RDCRN (Rare Diseases Clinical Research Network) Project 2
The purpose of this study is to learn more about the effects of midodrine and droxidopa, two medications used for the treatment of orthostatic hypotension (low blood pressure on standing), on the veins of the abdomen of patients with autonomic failure. The study will be conducted at Vanderbilt University Medical Center, and consists of 2 parts: a screening and 2 testing days. The total length of the study will be about 5 days. About 34 participants will be screened for the study.
Read the detailed description
Patients with multiple system atrophy, pure autonomic failure or Parkinson disease, and orthostatic hypotension will be studied in a randomized, double-blind, 2-arm parallel design to compare the effects of droxidopa and midodrine on stoke volume during head up tilt. A total of 34 participants will be enrolled in the study (17 patients in each arm).
Screening Procedures: Potential participants will be screened in the Vanderbilt Autonomic Dysfunction Center (ADC). Medications affecting blood pressure, blood volume and the autonomic nervous system such as pressor medications, fludrocortisone and carbidopa will be withdrawn for at least 5 half-lives before studies. Patients will undergo a complete history and physical examination, ECG, routine clinical laboratory analyses and a blood pregnancy test for women with childbearing potential. Autonomic testing including a tilt table testing and a posture study with plasma catecholamines is then performed to determine if they meet the inclusion/exclusion criteria.
Eligible participants will then be randomized to the droxidopa or the midodrine treatment group. All patients will be studied on two separate days, two days apart: one day with the active drug (droxidopa 300mg PO or midodrine 10mg PO) and one day with placebo.
On each study day, two tilt table tests will be performed. Patients will be instrumented to measure blood pressure and heart rate (continuously and intermittently), segmental impedance, cardiac output (inert gas rebreathing technique and/or impedance cardiography), and venous capacitance. Baseline measurements will then be taken in the supine position for about 30 minutes, and during head-up tilt for ≤10 minutes at 60 degrees. Supine baseline measurements will include the estimation of splanchnic venous capacitance. At the end of the head up tilt (HUT), patients will be asked to rate severity of their orthostatic symptoms.
Patients will then be placed in the seated position (time 0) and will receive a single oral dose of either droxidopa 300 mg or placebo, followed two hours later by a single oral dose of placebo or midodrine 10 mg. On the placebo day, both groups will receive a placebo pill at time 0 and at 2 hours. After ~3 hours of first drug administration, a second tilt table test will be performed, and outcome measurements will be repeated while supine and during HUT. The investigators may apply abdominal compression of 40 mmHg with an inflatable binder at the end of the second HUT. Outcome measurements will be repeated during 5 minutes of compression.
- Conditions
- Autonomic Failure, Pure Autonomic Failure, Multiple System Atrophy, Parkinson Disease, Orthostatic Hypotension
- Being tested
- Droxidopa, Midodrine, Placebo
- Keywords
- midodrine, droxidopa, splanchnic circulation
- Medical subject headings
- Pure Autonomic Failure, Multiple System Atrophy, Parkinson Disease, Hypotension, Orthostatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DroxidopaDrug
Also called Northera
Single oral dose 300 mg
MidodrineDrug
Single oral dose 10 mg
PlaceboDrug
sugar pill
| Study group | Role | What they receive |
|---|---|---|
| Droxidopa and Placebo | Experimental | Patients will be studied on two separate days, two days apart: one day with the active drug and one day with placebo. The order of the study days will be randomized. On each study day, patients will receive a single oral dose of either droxidopa 300 mg or placebo after the first tilt table test, followed two hours later by a single oral dose of placebo. Receives: Drug: Droxidopa; Drug: Placebo |
| Midodrine and Placebo | Experimental | Patients will be studied on two separate days, two days apart: one day with the active drug and one day with placebo. The order of the study days will be randomized. On each study day, patients will receive a single oral dose of placebo after the first tilt table test, followed two hours later by a single oral dose of either midodrine 10 mg or placebo. Receives: Drug: Midodrine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stroke volume
The primary outcome will be the percent change from supine in stroke volume during HUT
Measured: Up to 10 min of head up tilt
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2016 (estimated)
- Study startSep 2016
- Primary completionOct 2026
- Study completionOct 2026
Why it stopped: enrollment goal was not met.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autonomic FailureStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Italo Biaggioni, Vanderbilt University Medical Center
- Investigators
- Italo Biaggioni, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02897063
- Sponsor's protocol ID
- 160255
- Status last verified
- Oct 2026
- First submitted
- 7 Sep 2016
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure Aim 2 of RDCRN (Rare Diseases Clinical Research Network) Project 2
- ClinicalTrials.gov ID
- NCT02897063
- Acronym / sponsor ID
- 160255
- Conditions
- Autonomic Failure, Pure Autonomic Failure, Multiple System Atrophy, Parkinson Disease, Orthostatic Hypotension
- Keywords
- midodrine, droxidopa, splanchnic circulation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: enrollment goal was not met.
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- Oct 2026 (actual)
- Study completion
- Oct 2026 (actual)
- First posted
- 12 Sep 2016 (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 learn more about the effects of midodrine and droxidopa, two medications used for the treatment of orthostatic hypotension (low blood pressure on standing), on the veins of the abdomen of patients with autonomic failure. The study will be conducted at Vanderbilt University Medical Center, and consists of 2 parts: a screening and 2 testing days. The total length of the study will be about 5 days. About 34 participants will be screened for the study.
Detailed description
Patients with multiple system atrophy, pure autonomic failure or Parkinson disease, and orthostatic hypotension will be studied in a randomized, double-blind, 2-arm parallel design to compare the effects of droxidopa and midodrine on stoke volume during head up tilt. A total of 34 participants will be enrolled in the study (17 patients in each arm).
Screening Procedures: Potential participants will be screened in the Vanderbilt Autonomic Dysfunction Center (ADC). Medications affecting blood pressure, blood volume and the autonomic nervous system such as pressor medications, fludrocortisone and carbidopa will be withdrawn for at least 5 half-lives before studies. Patients will undergo a complete history and physical examination, ECG, routine clinical laboratory analyses and a blood pregnancy test for women with childbearing potential. Autonomic testing including a tilt table testing and a posture study with plasma catecholamines is then performed to determine if they meet the inclusion/exclusion criteria.
Eligible participants will then be randomized to the droxidopa or the midodrine treatment group. All patients will be studied on two separate days, two days apart: one day with the active drug (droxidopa 300mg PO or midodrine 10mg PO) and one day with placebo.
On each study day, two tilt table tests will be performed. Patients will be instrumented to measure blood pressure and heart rate (continuously and intermittently), segmental impedance, cardiac output (inert gas rebreathing technique and/or impedance cardiography), and venous capacitance. Baseline measurements will then be taken in the supine position for about 30 minutes, and during head-up tilt for ≤10 minutes at 60 degrees. Supine baseline measurements will include the estimation of splanchnic venous capacitance. At the end of the head up tilt (HUT), patients will be asked to rate severity of their orthostatic symptoms.
Patients will then be placed in the seated position (time 0) and will receive a single oral dose of either droxidopa 300 mg or placebo, followed two hours later by a single oral dose of placebo or midodrine 10 mg. On the placebo day, both groups will receive a placebo pill at time 0 and at 2 hours. After ~3 hours of first drug administration, a second tilt table test will be performed, and outcome measurements will be repeated while supine and during HUT. The investigators may apply abdominal compression of 40 mmHg with an inflatable binder at the end of the second HUT. Outcome measurements will be repeated during 5 minutes of compression.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Droxidopa and Placebo | Experimental | Drug: Droxidopa, Drug: PlaceboPatients will be studied on two separate days, two days apart: one day with the active drug and one day with placebo. The order of the study days will be randomized. On each study day, patients will receive a single oral dose of either droxidopa 300 mg or placebo after the first tilt table test, followed two hours later by a single oral dose of placebo. |
| Midodrine and Placebo | Experimental | Drug: Midodrine, Drug: PlaceboPatients will be studied on two separate days, two days apart: one day with the active drug and one day with placebo. The order of the study days will be randomized. On each study day, patients will receive a single oral dose of placebo after the first tilt table test, followed two hours later by a single oral dose of either midodrine 10 mg or placebo. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male and female subjects, age 40-80 years with possible or probable Multiple System Atrophy, Pure Autonomic Failure, or Parkinson disease, as defined by Consensus Criteria.
- Neurogenic orthostatic hypotension defined as a ≥30-mmHg decrease in systolic blood pressure within 3 minutes of standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes.
- Subjects able and willing to provide informed consent.
Key exclusion criteria (10 listed)
- Supine hypertension, defined as systolic blood pressure of ≥ 160 mmHg measured on two separate occasions.
- Pregnancy.
- Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathies, and autoimmune neuropathies.
- History of known aortic aneurisms, thoracic, abdominal or pelvic surgery in the past 6 months.
- Symptomatic abdominal or inguinal hernias.
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 |
|---|---|---|
| DroxidopaAlso: NortheraSingle oral dose 300 mg | Drug | Droxidopa and Placebo |
| MidodrineSingle oral dose 10 mg | Drug | Midodrine and Placebo |
| Placebosugar pill | Drug | Droxidopa and Placebo, Midodrine and Placebo |
Primary outcome
Stroke volume
Time frame: Up to 10 min of head up tilt
The primary outcome will be the percent change from supine in stroke volume during HUT
Results and safety
The study was stopped early (reason given: enrollment goal was not met.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2026.
- Individual participant dataSharing planned: No
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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.
Italo Biaggioni, MD principal investigator
Vanderbilt University Medical Center
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 Droxidopa and Midodrine in people with Autonomic Failure and Pure Autonomic Failure, 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 3 inclusion and 10 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 23 Oct 2026. 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 was stopped early (reason given: enrollment goal was not met.). Results are not available in the source record.
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?
Stroke volume (time frame: Up to 10 min of head up tilt). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Oct 2026.