Treatment of Orthostatic Hypotension

Phase 2

Terminated

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

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Droxidopa	Droxidopa Oral Product	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.

Primary Outcome Measures

Name	Time	Method
Change in Systolic Blood Pressure With Standing	Up to 240 minutes post dose on Study Days 1, 2, 3 and 4.	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.

Secondary Outcome Measures