Effect of Midodrine vs Abdominal Compression on Cardiovascular Risk Markers in Autonomic Failure Patients

The purpose of this study is to learn more about the effects of abdominal compression and the medication midodrine, two interventions used for the treatment of orthostatic hypotension (low blood pressure on standing), on hemodynamic markers of cardiovascular risk. The study will be conducted at the Vanderbilt University Medical Center and consists of a screening and 2 testing days, one with abdominal compression and one with midodrine. The total length of the study will be about 5 days.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Multiple System Atrophy; Neurogenic Orthostatic Hypotension; Pure Autonomic Failure; Autonomic Failure
• Intervention / Treatment: Drug: Midodrine; Device: sham compression; Drug: Placebo pill; Device: Abdominal compression

Detailed Description

The study includes up to 5 days spent in the Vanderbilt University Medical Center, at least one day of screening tests, followed by 2 study days.

Screening tests include a physical examination and history, routine safety laboratory assessments, and testing of the autonomic nervous system. Medications affecting blood pressure and the autonomic nervous system such as pressor medications will be withdrawn for at least 5 half-lives before studies, except for fludrocortisone. Other medications will be held constant throughout the study.

Eligible participants will then be studied on two separate days in random order: one day with midodrine combined with sham abdominal compression, and one day with abdominal compression combined with a placebo pill.

On each study day, participants will be instrumented to measure blood pressure, heart rate, hemodynamic parameters, segmental impedance, and markers of cardiovascular risk. A baseline tilt table test will be performed to obtain supine and upright baseline measurements, including the assessment of orthostatic symptoms. Participants will then receive a single oral dose of placebo or midodrine, and a deflated binder will be placed around the abdomen. Thirty to sixty minutes later, a second tilt table test will be done with sham or active abdominal compression. Outcome measurements will be repeated in the supine and upright positions. At the end of the second tilt table test, the investigators may also assess splanchnic venous capacitance.

• Study Type: Interventional
• Enrollment (Estimated): 31
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Luis Okamoto, MD; Phone Number: 615-936-6119; Email: luis.e.okamoto@vumc.org
• Study Contact Backup: Name: Bonnie K Black, RN; Phone Number: 615-343-6862; Email: bonnie.black@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Emily C Smith, RN BSN MPH; Phone Number: 615-875-1516; Email: emily.c.smith@vumc.org
      • Contact: Luis E Okamoto, MD; Phone Number: 6159366119; Email: luis.e.okamoto@vumc.org
      • Sub-Investigator: Andre Diedrich, MD PhD
      • Sub-Investigator: Emily C Smith, RN MPH
      • Sub-Investigator: Alfredo Gamboa, MD
      • Sub-Investigator: Cyndya A Shibao, MD
      • Principal Investigator: Luis E Okamoto, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female subjects, age 40-80 years, with autonomic failure including pure autonomic failure, multiple system atrophy and Parkinson disease.
• Neurogenic orthostatic hypotension, defined as a ≥20-mmHg decrease in SBP within 3 minutes of standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes.
• Patients who are willing and able to provide informed consent

Exclusion Criteria:

• Pregnancy.
• Patients with any contraindication or intolerant to abdominal compression including history of aortic aneurysms, thoracic, abdominal or pelvic surgery within 6 months of study participation; symptomatic abdominal or inguinal hernias; severe gastrointestinal 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.
• Pre-existing sustained supine hypertension ≥180/110mmHg
• Bedridden patients or those who are unable to stand due to motor impairment or severe OH.
• Patients who cannot tolerate the medication withdrawal, defined as those who are unable to stand for at least one minute after the medication withdrawal period or those with sustained supine hypertension ≥180/110mmHg.
• Clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months.
• Clinically significant pulmonary, renal, hematopoietic, hepatic disease, or 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Midodrine; Single oral dose of midodrine (5-10mg) combined with sham abdominal compression	Drug: Midodrine; Midodrine 5-10 mg, single oral dose; Device: sham compression; Sham abdominal compression during head-up tilt
Experimental: Abdominal Compression; Abdominal compression (up to 40 mmHg) combined with a placebo pill	Drug: Placebo pill; single oral dose; Other Names: sugar pill; Device: Abdominal compression; abdominal compression up to 40 mmHg during head-up tilt

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic markers of cardiovascular risk	augmentation index, central blood pressure, pulse wave velocity	1 hour post-intervention tilt table test

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Luis Okamoto, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 27, 2020
• First Submitted That Met QC Criteria: November 2, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 24, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: midodrine; arterial stiffness; splanchnic circulation; abdominal binder
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Parkinson Disease; Hypotension; Multiple System Atrophy; Shy-Drager Syndrome; Hypotension, Orthostatic; Pure Autonomic Failure; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Midodrine
• Other Study ID Numbers: 201649; 1R01HL144568-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No