Hemodynamic Mechanisms of Abdominal Compression in the Treatment of Orthostatic Hypotension in Autonomic Failure

Compression garments have been shown to be effective in the treatment of orthostatic hypotension in autonomic failure patients. The purpose of this study is to determine the hemodynamic mechanisms by which abdominal compression (up to 40 mm Hg) improve the standing blood pressure and orthostatic tolerance in these patients, and to compare them with those of the standard of care midodrine. The investigators will test the hypothesis that abdominal compression will blunt the exaggerated fall in stroke volume and the increase in abdominal vascular volume during head up tilt.

Study Overview

• Status: Recruiting
• Conditions: Multiple System Atrophy; Orthostatic Hypotension; Pure Autonomic Failure; Autonomic Failure
• Intervention / Treatment: Other: Abdominal compression; Drug: Placebo pill; Other: Sham abdominal compression; Drug: midodrine

Detailed Description

Patients with autonomic failure are characterized by disabling orthostatic hypotension (low blood pressure on standing) due to severe impairment of the autonomic nervous system. Compression garments such as waist-high stockings and abdominal binders have been shown to improve orthostatic hypotension in these patients. The purpose of this study is to determine the hemodynamic mechanisms by which abdominal compression (up to 40 mm Hg) improve the standing blood pressure and orthostatic tolerance in these patients, and to compare them with those of the standard of care midodrine. The investigators will test the hypothesis that abdominal compression will blunt the exaggerated fall in stroke volume and the increase in abdominal vascular volume during head up tilt. This study will help us better understand the contribution of the abdominal veins to orthostatic hypotension and the mechanisms underlying this non-pharmacological therapeutic approach.

Participants will be studied in a tilt table in two separate days in a randomized, crossover fashion with sham abdominal compression (~5 mmHg) and active compression (~40 mmHg).

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 1

Contacts and Locations

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

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University
      • Sub-Investigator: Andre Diedrich, MD/PhD
      • Contact: Emily C Smith, RN; Phone Number: 615-875-1516; Email: autonomics@vumc.org
      • Contact: Bonnie K Black, RN; Phone Number: 615-322-3304; Email: autonomics@vumc.org
      • Sub-Investigator: Alfredo Gamboa, MD
      • Sub-Investigator: Cyndya A Shibao, MD
      • Sub-Investigator: Italo Biaggioni, MD
      • Principal Investigator: Luis E Okamoto, MD
      • Sub-Investigator: Emily C Smith, RN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female patients,
• between 18-80 yrs.,
• with neurogenic orthostatic hypotension associated with primary autonomic failure (Parkinson Disease, Multiple System Atrophy and Pure Autonomic Failure). Orthostatic hypotension will be defined as ≥20 mmHg decrease in systolic BP or ≥10 mmHg of diastolic BP within 3 minutes on standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes (Freeman et al., 2011).
• Patients able and willing to provide informed consent.

Exclusion Criteria:

• Pregnancy.
• Significant cardiac, renal or hepatic illness, or with contraindications to administration of pressor agents or external abdominal compression will be excluded.
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abdominal compression and placebo pill; Abdominal compression with an inflatable abdominal binder (up to 40 mmHg) during head up tilt, and placebo pill given 1 hour before the second head up tilt	Other: Abdominal compression; Abdominal compression of 40 mmHg with a commercial inflatable cuff applied during head up tilt; Other Names: abdominal binder; Drug: Placebo pill; Placebo pill given 1 hour before the second heat up tilt
Sham Comparator: Sham abdominal compression and placebo; Sham abdominal compression with an inflatable abdominal binder (~5 mmHg) during head up tilt, and placebo pill given 1 hour before the second head up tilt	Drug: Placebo pill; Placebo pill given 1 hour before the second heat up tilt; Other: Sham abdominal compression; Sham abdominal compression of 5 mmHg with a commercial inflatable cuff applied during head up tilt; Other Names: abdominal binder
Experimental: Abdominal compression and midodrine; Abdominal compression with an inflatable abdominal binder (up to 40 mmHg) during head up tilt, and midodrine 2.5-10 mg PO given 1 hour before the second head up tilt	Other: Abdominal compression; Abdominal compression of 40 mmHg with a commercial inflatable cuff applied during head up tilt; Other Names: abdominal binder; Drug: midodrine; Midodrine single dose 2.5-10mg PO given 1 hour before the second head up tilt; Other Names: ProAmatine
Active Comparator: Sham abdominal compression and midodrine; Sham abdominal compression with an inflatable abdominal binder (~5 mmHg) during head up tilt, and midodrine 2.5-10mg PO given 1 hour before the second head up tilt	Other: Sham abdominal compression; Sham abdominal compression of 5 mmHg with a commercial inflatable cuff applied during head up tilt; Other Names: abdominal binder; Drug: midodrine; Midodrine single dose 2.5-10mg PO given 1 hour before the second head up tilt; Other Names: ProAmatine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke volume	Percent change from supine in stroke volume during head up tilt	an average of 15 minutes of head up tilt

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure	Change from baseline in systolic blood pressure during head up tilt	an average of 15 minutes of head up tilt
Splanchnic vascular volume	Percent change from supine in splanchnic vascular volume during head up tilt.	an average of 15 minutes of head up tilt

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 21, 2015
• First Submitted That Met QC Criteria: April 23, 2015
• First Posted (Estimated): April 29, 2015

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: treatment; orthostatic hypotension; autonomic failure; compression garments
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; 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: 140634; 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: No
• Studies a U.S. FDA-regulated device product: No