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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Orthostatic Hypotension, Pure Autonomic Failure, Multiple System Atrophy, Autonomic Failure

Intervention / Treatment
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* Other: Abdominal compression
* Other: Sham abdominal compression
* Drug: Placebo pill
* Drug: midodrine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autonomic failure, orthostatic hypotension, compression garments, treatment