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

Primary Purpose

Neurogenic Orthostatic Hypotension, Autonomic Failure, Pure Autonomic Failure

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Midodrine

Placebo pill

Abdominal compression

sham compression

About this trial

This is an interventional other trial for Neurogenic Orthostatic Hypotension focused on measuring midodrine, abdominal binder, splanchnic circulation, arterial stiffness

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Vanderbilt University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Midodrine

Abdominal Compression

Arm Description

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

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

Outcomes

Primary Outcome Measures

Hemodynamic markers of cardiovascular risk

augmentation index, central blood pressure, pulse wave velocity

Secondary Outcome Measures

Full Information

NCT ID

NCT04620382

First Posted

October 27, 2020

Last Updated

March 17, 2023

Sponsor

Vanderbilt University Medical Center

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT04620382

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 9, 2020 (Actual)

Primary Completion Date

September 1, 2024 (Anticipated)

Study Completion Date

December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt University Medical Center

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

midodrine, abdominal binder, splanchnic circulation, arterial stiffness

7. Study Design

Primary Purpose

Other

Study Phase

Early Phase 1

Interventional Study Model

Crossover Assignment

Model Description

Randomized, single-blind, crossover

Masking

Participant

Masking Description

placebo pill and sham abdominal compression will be used

Allocation

Randomized

Enrollment

31 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Midodrine

Arm Type

Active Comparator

Arm Description

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

Arm Title

Abdominal Compression

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Midodrine

Intervention Description

Midodrine 5-10 mg, single oral dose

Intervention Type

Drug

Intervention Name(s)

Placebo pill

Other Intervention Name(s)

sugar pill

Intervention Description

single oral dose

Intervention Type

Device

Intervention Name(s)

Abdominal compression

Intervention Description

abdominal compression up to 40 mmHg during head-up tilt

Intervention Type

Device

Intervention Name(s)

sham compression

Intervention Description

Sham abdominal compression during head-up tilt

Primary Outcome Measure Information:

Title

Hemodynamic markers of cardiovascular risk

Description

augmentation index, central blood pressure, pulse wave velocity

Time Frame

1 hour post-intervention tilt table test

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Emily C Smith, RN

Phone

615-875-1516

emily.c.smith@vumc.org

First Name & Middle Initial & Last Name or Official Title & Degree

Luis Okamoto, MD

Phone

615-936-6119

luis.e.okamoto@vumc.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Luis Okamoto, MD

Organizational Affiliation

Vanderbilt University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Emily C Smith, RN BSN MPH

Phone

615-875-1516

emily.c.smith@vumc.org

First Name & Middle Initial & Last Name & Degree

Luis E Okamoto, MD

Phone

6159366119

luis.e.okamoto@vumc.org

First Name & Middle Initial & Last Name & Degree

Luis E Okamoto, MD

First Name & Middle Initial & Last Name & Degree

Andre Diedrich, MD PhD

First Name & Middle Initial & Last Name & Degree

Alfredo Gamboa, MD

First Name & Middle Initial & Last Name & Degree

Cyndya A Shibao, MD

First Name & Middle Initial & Last Name & Degree

Emily C Smith, RN MPH

12. IPD Sharing Statement

Plan to Share IPD

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

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