Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02897063|
Recruitment Status : Recruiting
First Posted : September 12, 2016
Last Update Posted : September 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Autonomic Failure Pure Autonomic Failure Multiple System Atrophy Parkinson Disease Orthostatic Hypotension||Drug: Droxidopa Drug: Midodrine Drug: Placebo||Phase 1|
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blood volume and the autonomic nervous system such as pressor medications, fludrocortisone and carbidopa will be withdrawn for at least 5 half-lives before studies.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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||34 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Basic Science|
|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|
|Study Start Date :||September 2016|
|Estimated Primary Completion Date :||March 2021|
|Estimated Study Completion Date :||August 2021|
Experimental: Droxidopa and Placebo
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.
Single oral dose 300 mg
Other Name: Northera
Experimental: Midodrine and Placebo
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.
Single oral dose 10 mg
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02897063
|Contact: Emily C Smith, RNfirstname.lastname@example.org|
|Contact: Bonnie K Black, RNemail@example.com|
|United States, Tennessee|
|Autonomic Dysfunction Center/ Vanderbilt University Medical Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Emily C Smith, RN 615-875-1516 firstname.lastname@example.org|
|Contact: Bonnie K Black, RN 615-322-3304 email@example.com|
|Sub-Investigator: Bonnie K Black, RN|
|Sub-Investigator: Luis E Okamoto, MD|
|Sub-Investigator: David Robertson, MD|
|Principal Investigator: Italo Biaggioni, MD|
|Sub-Investigator: Alfredo Gamboa, MD|
|Sub-Investigator: Cyndya A Shibao, MD|
|Sub-Investigator: Andre Diedrich, MD, PhD|
|Sub-Investigator: Emily C Smith, RN|
|Principal Investigator:||Italo Biaggioni, MD||Vanderbilt University Medical Center|