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

Vanderbilt University Medical Center

Status and phase: Enrolling; Phase 1

Conditions: Autonomic Failure; Multiple System Atrophy; Pure Autonomic Failure; Orthostatic Hypotension

Treatments: Other: Abdominal compression; Other: Sham abdominal compression; Drug: midodrine; Drug: Placebo pill

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02429557

1R01HL144568-01A1 (U.S. NIH Grant/Contract)

140634

Details and patient eligibility

About

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.

Full 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).

Enrollment: 29 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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29 participants in 4 patient groups

Abdominal compression and placebo pill

Experimental group

Description:

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

Treatment:

Drug: Placebo pill

Other: Abdominal compression

Sham abdominal compression and placebo

Sham Comparator group

Description:

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

Treatment:

Drug: Placebo pill

Other: Sham abdominal compression

Abdominal compression and midodrine

Experimental group

Description:

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

Treatment:

Drug: midodrine

Other: Abdominal compression

Sham abdominal compression and midodrine

Active Comparator group

Description:

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

Treatment:

Drug: midodrine

Other: Sham abdominal compression