Treatment of Orthostatic Hypotension

Study Overview
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Brief Summary
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The purpose of this study is to try different medications in patients with low blood pressure and other problems with their involuntary (autonomic) nervous system. The pharmacological trials in this study will perhaps lead to more effective treatment. The protocol includes single dose trials, dose-selection trials, 5-day trials and chronic (approximately 2 months) trials, although only dose-selection trials were consistently performed and have results presented.

Detailed Description
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We see many patients at the Autonomic Dysfunction Center who can be given a fairly definitive diagnosis, e.g., Orthostatic Intolerance, Pure Autonomic Failure, Multiple System Atrophy, and Baroreflex Failure. However, some patients present with a unique constellation of symptoms of autonomic dysfunction so that they do not fit into a diagnostic category. We hypothesize that a genetic cause exists in some of these patients. We further propose that our comprehensive evaluation of these patients will provide us with information on the pathophysiology of their condition and assist us in optimizing their treatment.

Official Title
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Treatment of Hypotensive Patients Having a Unique Pattern of Autonomic Symptoms

Conditions
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Autonomic Nervous System Diseases, Orthostatic Hypotension, Dopamine Beta-Hydroxylase Deficiency, Orthostatic Intolerance

Intervention / Treatment
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* Drug: Droxidopa Oral Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with severe orthostatic hypotension and other autonomic symptoms who do not meet criteria for one of our standard diagnoses non-smokers drug-free able to give informed consent free of pulmonary, renal, hematopoietic, hepatic and cardiac disease Exclusion Criteria: medications affecting the autonomic nervous system any chronic illness (cardiac, pulmonary, endocrine, gastrointestinal, rheumatologic) anemia (Hct < 30) women of childbearing age who are pregnant or nursing smokers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Interventional Model Description: Although the study was designed as a potential trial of multiple medications, plus placebo, in actuality it served as a means of safely determining the optimal dose of Droxidopa for our patients with Dopamine beta-Hydroxylase Deficiency to take at home. Before each dose of Droxidopa, blood pressure and heart rate were measured for 30 minutes. At 60 or 120 minutes after dosing, blood pressure was also measured after 5 minutes of lying down and 5 minutes of sitting or standing. These measurements were used to calculate the orthostatic change in systolic blood pressure, the primary outcome.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Droxidopa<br>Patients with known or suspected Dopamine beta-Hydroxylase Deficiency were administered Droxidopa doses of 25 mg, 50 mg, 100 mg, 200 mg, 250 mg or 300 mg up to three times daily. Supine and upright blood pressures were subsequently measured 60 to 240 minutes post-dose. | Drug: Droxidopa Oral Product<br>* Droxidopa administered in increasing dosages up to 300 mg<br>* Other names: L-DOPS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Systolic Blood Pressure With Standing | The difference between upright and supine systolic blood pressures (dSBP; upright - supine) was calculated for each patient at 60-240 minutes after each dose of droxidopa. For each post-dose timepoint and study day, the average of up to three blood pressure readings per droxidopa dose was calculated. Dosing is individualized for each patient based upon how well the drug is tolerated and the degree of improvement in orthostatic vital signs and symptoms following drug administration. The dosages administered, as well as the number of timepoints and days, therefore, varied between patients. | Up to 240 minutes post dose on Study Days 1, 2, 3 and 4. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autonomic nervous system diseases, blood pressure, congenital, orthostasis, catecholamines