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

Phase 1
Recruiting
Conditions
Multiple System Atrophy
Orthostatic Hypotension
Autonomic Failure
Pure Autonomic Failure
Interventions
Other: Abdominal compression
Other: Sham abdominal compression
Drug: Placebo pill
Registration Number
NCT02429557
Lead Sponsor
Vanderbilt University Medical Center
Brief Summary

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.

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).

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
29
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Abdominal compression and midodrineAbdominal compressionAbdominal 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
Sham abdominal compression and midodrineSham abdominal compressionSham 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
Sham abdominal compression and placeboPlacebo pillSham 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
Abdominal compression and placebo pillAbdominal compressionAbdominal 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
Abdominal compression and placebo pillPlacebo pillAbdominal 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
Sham abdominal compression and placeboSham abdominal compressionSham 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
Abdominal compression and midodrinemidodrineAbdominal 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
Sham abdominal compression and midodrinemidodrineSham 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
Primary Outcome Measures
NameTimeMethod
Stroke volumean average of 15 minutes of head up tilt

Percent change from supine in stroke volume during head up tilt

Secondary Outcome Measures
NameTimeMethod
Systolic blood pressurean average of 15 minutes of head up tilt

Change from baseline in systolic blood pressure during head up tilt

Splanchnic vascular volumean average of 15 minutes of head up tilt

Percent change from supine in splanchnic vascular volume during head up tilt.

Trial Locations

Locations (1)

Vanderbilt University

🇺🇸

Nashville, Tennessee, United States

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