Keywords: Symptomatic nOH , Parkinson's Disease (PD) , Multiple System Atrophy (MSA) , Pure Autonomic Failure (PAF) , Dopamine Beta Hydroxylase (DBH) , PHOENIX , Droxidopa , Orthostatic hypotension
IRB Number: 00071707
Specialty: Neurology, Neurology, Neurology, Neurology, Neurology
Sub Specialties: Multiple System Atrophy, Movement Disorders, Parkinson's Disease, Neurodegenerative Disorders
The purpose of this research study is to determine whether a drug called droxidopa can relieve the symptoms of nOH and whether it causes any side effects in people with symptomatic nOH over a long-term (17 weeks) treatment period. Droxidopa is a drug that is changed in the body to a chemical called norepinephrine. Norepinephrine is a chemical in your body that is used by your nervous system to signal nerves that control blood pressure.
BACKGROUND Systolic blood pressure (SBP) is transiently and minimally decreased in healthy individuals upon standing. Normal physiologic feedback mechanisms work through neurally-mediated pathways to maintain the standing blood pressure (BP), and thus maintain adequate cerebral perfusion. The compensatory mechanisms that regulate BP upon standing are dysfunctional in patients with orthostatic hypotension (OH), a condition that may lead to inadequate cerebral perfusion with accompanying symptoms of syncope, dizziness or lightheadedness, unsteadiness and blurred or impaired vision, among other symptoms. Orthostatic hypotension may be a severely disabling condition which can seriously interfere with the quality of life of afflicted patients. Currently available therapeutic options provide some symptomatic relief in a subset of patients, but are relatively ineffective and are often accompanied by severe side effects that limit their usefulness. Support garments (e.g., tight-fitting leotards) may prove useful in some patients, but are difficult to don without family or nursing assistance, especially for older patients. Midodrine, fludrocortisone, methylphenidate, ephedrine, indomethacin and dihydroergotamine are some of the pharmacological interventions that have been used to treat orthostatic hypotension, although only midodrine is specifically approved for this indication. The limitations of these currently available therapeutic options, and the incapacitating nature and often progressive downhill course of disease, point to the need for an improved therapeutic alternative. Droxidopa Droxidopa [also, known as L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS, or L-DOPS] is the International Non-proprietary Name (INN) for a synthetic amino acid precursor of norepinephrine (NE), which was originally developed by Sumitomo Pharmaceuticals Co., Limited, Japan. It has been approved for use in Japan since 1989. Droxidopa has been shown to improve symptoms of orthostatic hypotension that result from a variety of conditions including Shy-Drager syndrome (Multiple System Atrophy), Pure Autonomic Failure (PAF), and Parkinson’s disease (PD). There are four stereoisomers of DOPS; however, only the L-threoenantiomer (droxidopa) is biologically active.
Principal Investigator: David Shprecher