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Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure

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ClinicalTrials.gov Identifier: NCT02897063
Recruitment Status : Recruiting
First Posted : September 12, 2016
Last Update Posted : February 4, 2019
Sponsor:
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University

Tracking Information
First Submitted Date  ICMJE September 7, 2016
First Posted Date  ICMJE September 12, 2016
Last Update Posted Date February 4, 2019
Study Start Date  ICMJE September 2016
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2016)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02897063 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure
Official Title  ICMJE The Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure Aim 2 of RDCRN (Rare Diseases Clinical Research Network) Project 2
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE
  • Autonomic Failure
  • Pure Autonomic Failure
  • Multiple System Atrophy
  • Parkinson Disease
  • Orthostatic Hypotension
Intervention  ICMJE
  • Drug: Droxidopa
    Single oral dose 300 mg
    Other Name: Northera
  • Drug: Midodrine
    Single oral dose 10 mg
  • Drug: Placebo
    sugar pill
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Droxidopa
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Midodrine
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 9, 2016)
34
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Emily C Smith, RN 615.875.1516 autonomics@vumc.org
Contact: Bonnie K Black, RN 615-343-6862 autonomics@vumc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02897063
Other Study ID Numbers  ICMJE 160255
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Italo Biaggioni, Vanderbilt University
Study Sponsor  ICMJE Vanderbilt University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Italo Biaggioni, MD Vanderbilt University Medical Center
PRS Account Vanderbilt University Medical Center
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP