Automated Abdominal Binder for Orthostatic Hypotension

Study Overview
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Brief Summary
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The automated inflatable abdominal binder is an investigational device for the treatment of orthostatic hypotension (low blood pressure on standing) in patients with autonomic failure. The purpose of this study is to determine safety and effectiveness of the automated abdominal binder in improving orthostatic tolerance in these patients.

Detailed Description
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This is a randomized, double-blind, sham-controlled, parallel group study to compare the efficacy of the automated abdominal binder (inflated to 40 mm Hg) versus sham treatment (abdominal binder inflated to 5 mm Hg) in improving orthostatic tolerance in patients with primary autonomic failure disabled by orthostatic hypotension. Potential participants will be admitted to the Vanderbilt Clinical Research Center for evaluation of inclusion and exclusion criteria. Eligible patients will be randomized to the active or sham binder group. Patients will then be asked to participate on three separate study days, two days apart: one day for baseline measurements (placebo pill t.i.d), one day for treatment with 10 mg midodrine t.i.d (standard of care), and one day for treatment with active or sham binder combined with placebo pill t.i.d. The order of the study days will be randomized. On each study day, blood pressure and heart rate will be measured while sitting, lying down, standing and walking during the Morning Orthostatic Trial, and posture and walking tests.

Official Title
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Randomized, Double-blind, Sham-controlled to Evaluate the Effects of an Automated Abdominal Binder in Improving Orthostatic Tolerance in Autonomic Failure Patients With Disabling Orthostatic Hypotension

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

Intervention / Treatment
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* Device: automated abdominal binder
* Device: Sham binder
* Drug: Placebo
* Drug: Midodrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects, age 40-80 years. Possible or probable Multiple Systems Atrophy and Pure Autonomic Failure as defined by Consensus Criteria. Neurogenic orthostatic hypotension defined as a ≥30-mm Hg decrease in SBP within 3 minutes of standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes, and Moderate to severe orthostatic symptoms, defined as an Orthostatic Hypotension Symptom Assessment (OHSA) composite score ≥4 (self-rating Likert scale of 0 to 10, with 0 reflecting absence of symptoms), within the first 10 minutes of the screening orthostatic stress test, and that have an impact in quality of life, as defined by the patient. Able and willing to provide informed consent. Exclusion Criteria: Pregnancy. Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathies, and autoimmune neuropathies. History of known aortic aneurisms, thoracic, abdominal or pelvic surgery in the past 6 months; symptomatic abdominal or inguinal hernias; severe gastroesophageal reflux; recent fractures or fissures of ribs, thoracic or lumbar spine; medical devices implanted on the abdominal wall or abdomen that would interfere with the binder; known abdominal or pelvic tumors, cysts or enlarged spleen; intolerance to any increase in intraabdominal pressure. Pre-existing sustained supine hypertension ≥180/110. Bedridden patients or those who are unable to stand due to motor impairment or severe orthostatic hypotension. Clinically unstable coronary artery disease (recurrent angina despite medical therapy), or major cardiovascular or neurological event in the past 6 months (myocardial infarction, stroke or transient ischemic attacks). Concomitant use of anticoagulants

Ages Eligible for Study
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Minimum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, sham-controlled, parallel-group, 3-study days inpatient study to compare the efficacy of the automated abdominal binder versus sham treatment in improving orthostatic tolerance in patients with primary autonomic failure disabled by neurogenic orthostatic hypotension.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Automated Abdominal Binder<br>Participants will be studied on three separate study days, two days apart: one day for baseline measurements (placebo pill t.i.d), one day for treatment with 10 mg midodrine t.i.d (standard of care), and one day for treatment with the automated abdominal binder combined with placebo pill t.i.d The automated abdominal binder will be placed during the morning orthostatic trial on the active/sham binder study day. The binder will inflate automatically ( 40 mmHg) every time the participant stands up throughout the study day. | Device: automated abdominal binder<br>* The binder automatically inflates every time the participant stands up to apply a compression level of about 40 mmHg. Participants will wear the device throughout the active/sham study day.<br>Drug: Placebo<br>* Oral placebo will be given three times a day on the baseline day (placebo)<br>Drug: Midodrine<br>* A midodrine pill 10mg will be given three times a day on the standard of care study day<br>|
| Sham Comparator: Sham binder<br>Participants will be studied on three separate study days, two days apart: one day for baseline measurements (placebo pill t.i.d), one day for treatment with 10 mg midodrine t.i.d (standard of care), and one day for treatment with the sham binder combined with placebo pill t.i.d. The sham binder will be placed during the morning orthostatic trial on the active/sham binder study day. The sham binder will inflate automatically ( 5 mmHg) every time the participant stands up throughout the study day. | Device: Sham binder<br>* The binder automatically inflates every time the participant stands up to apply a compression level of about 5 mmHg. Participants will wear the device throughout the active/sham study day.<br>Drug: Placebo<br>* Oral placebo will be given three times a day on the baseline day (placebo)<br>Drug: Midodrine<br>* A midodrine pill 10mg will be given three times a day on the standard of care study day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Orthostatic tolerance | orthostatic tolerance is defined as the area under the curve of the upright systolic blood pressure (AUCSBP) during the Morning Orthostatic Trials | After 10 minutes of standing (or as tolerated) during the Morning orthostatic trial on the automated binder/sham study day | 
| Orthostatic Hypotension Symptom Assessment (OHSA) Score | The Orthostatic Hypotension Symptom Assessment (OHSA) Score is the part I of the Orthostatic Hypotension Questionnaire (OHQ). It consists of six questions, each rating the intensity of one characteristic symptom of orthostatic hypotension: 1. Dizziness, lightheadedness, feeling faint, or feeling like you might black out; 2. Problems with vision (blurring, seeing spots, tunnel vision, etc.); 3. Generalized weakness; 4. Fatigue; 5. Trouble concentrating; and 6. Head/neck discomfort.The items are scored on an 11-point Likert scale from 0 to 10, with 0 indicating no symptoms and 10 indicating the worst possible symptoms. Composite score is the average of the item scores obtained at the post-intervention stand period during the Morning Orthostatic Trials | After 10 minutes of standing (or as tolerated) during the Morning orthostatic trial on the automated binder/sham study day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upright time | Sum of standing and walking times | After 10 minutes of standing and 15 minutes waking (as tolerated) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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orthostatic hypotension, abdominal binder, pure autonomic failure, multiple system atrophy