Autonomic Failure, Multiple System Atrophy, Orthostatic Hypotension, Pure Autonomic Failure
Conditions
Keywords
autonomic failure, orthostatic hypotension, compression garments, treatment
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).
Interventions
Abdominal compression of 40 mmHg with a commercial inflatable cuff applied during head up tilt
OTHERSham abdominal compression
Sham abdominal compression of 5 mmHg with a commercial inflatable cuff applied during head up tilt
DRUGPlacebo pill
Placebo pill given 1 hour before the second heat up tilt
DRUGmidodrine
Midodrine single dose 2.5-10mg PO given 1 hour before the second head up tilt
Sponsors
Vanderbilt University Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stroke volume | an average of 15 minutes of head up tilt | Percent change from supine in stroke volume during head up tilt |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systolic blood pressure | an average of 15 minutes of head up tilt | Change from baseline in systolic blood pressure during head up tilt |
| Splanchnic vascular volume | an average of 15 minutes of head up tilt | Percent change from supine in splanchnic vascular volume during head up tilt. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORItalo Biaggioni, MD
Vanderbilt University
PRINCIPAL_INVESTIGATORLuis E Okamoto, MD
Vanderbilt University Medical Center
Outcome results
None listed