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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04620382
• Other study ID #: 201649
• Secondary ID: 1R01HL144568-01A
• Status: Recruiting
• Phase: Early Phase 1
• Start date: November 9, 2020
• Est. completion date: December 1, 2024

Study information

• Verified date: March 2024
• Source: Vanderbilt University Medical Center
• Contact: Bonnie K Black, RN
• Phone: 615-343-6862
• Email: bonnie.black[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 Medications affecting blood pressure and the autonomic nervous system such as pressor medications will be withdrawn for at least 5 half-lives before studies, except for fludrocortisone.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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 31
• Est. completion date: December 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Autonomic Failure
• Hypotension
• Hypotension, Orthostatic
• Multiple System Atrophy
• Neurogenic Orthostatic Hypotension
• Parkinson Disease
• Pure Autonomic Failure
• Shy-Drager Syndrome

Intervention

Drug:
• Midodrine
Midodrine 5-10 mg, single oral dose
• Placebo pill
single oral dose

Device:
• Abdominal compression
abdominal compression up to 40 mmHg during head-up tilt
• sham compression
Sham abdominal compression during head-up tilt

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemodynamic markers of cardiovascular risk	augmentation index, central blood pressure, pulse wave velocity	1 hour post-intervention tilt table test