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

NCT ID: NCT04620382

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-09
• Study Completion Date: 2026-12-01

Brief Summary

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.

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 Medications affecting blood pressure and the autonomic nervous system such as pressor medications will be withdrawn for at least 5 half-lives before studies, except for fludrocortisone.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.

Conditions

Neurogenic Orthostatic Hypotension; Autonomic Failure; Pure Autonomic Failure; Multiple System Atrophy; Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

Midodrine

Single oral dose of midodrine (5-10mg) combined with sham abdominal compression

Group Type: ACTIVE_COMPARATOR

Midodrine

Intervention Type: DRUG

Midodrine 5-10 mg, single oral dose

sham compression

Intervention Type: DEVICE

Sham abdominal compression during head-up tilt

Abdominal Compression

Abdominal compression (up to 40 mmHg) combined with a placebo pill

Group Type: EXPERIMENTAL

Placebo pill

Intervention Type: DRUG

single oral dose

Abdominal compression

Intervention Type: DEVICE

abdominal compression up to 40 mmHg during head-up tilt

Interventions

Midodrine

Midodrine 5-10 mg, single oral dose

Intervention Type: DRUG

Placebo pill

single oral dose

Intervention Type: DRUG

Abdominal compression

abdominal compression up to 40 mmHg during head-up tilt

Intervention Type: DEVICE

sham compression

Sham abdominal compression during head-up tilt

Intervention Type: DEVICE

Other Intervention Names

sugar pill

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Luis E Okamoto

Research Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Luis Okamoto, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Bonnie K Black, RN

Role: CONTACT

bonnie.black@vumc.org

615-343-6862

Luis Okamoto, MD

Role: CONTACT

luis.e.okamoto@vumc.org

615-936-6119

Facility Contacts

Emily C Smith, RN BSN MPH

Role: primary

emily.c.smith@vumc.org

6158751516

Luis E Okamoto, MD

Role: backup

luis.e.okamoto@vumc.org

6159366119

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01HL144568-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

201649

Identifier Type: -

Identifier Source: org_study_id