Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)
- Conditions
- Non-diabetic NeuropathyPrimary Autonomic FailureDopamine Beta Hydroxylase DeficiencySymptomatic Neurogenic Orthostatic Hypotension (NOH)
- Interventions
- Drug: Placebo
- Registration Number
- NCT00633880
- Lead Sponsor
- Chelsea Therapeutics
- Brief Summary
The purpose of this study is to see whether droxidopa is effective in treating symptoms of neurogenic orthostatic hypotension in patients with Primary Autonomic Failure (Pure Autonomic Failure, Multiple System Atrophy, Parkinson's Disease), Non-diabetic neuropathy, or Beta Hydroxylase deficiency.
- Detailed Description
Systolic blood pressure 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, and thus maintain adequate cerebral perfusion. The compensatory mechanisms that regulate blood pressure upon standing are dysfunctional in subjects 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.
The autonomic nervous system has a central role in the regulation of blood pressure. Primary Autonomic Failure is manifested in a variety of syndromes. Orthostatic hypotension is a usual presenting symptom. Primary Autonomic Failure may be the primary diagnosis, and classifications include pure autonomic failure (PAF), also called idiopathic orthostatic hypotension (Bradbury-Eggleston syndrome) autonomic failure with multiple system atrophy (Shy-Drager syndrome) and also Parkinson's disease. Regardless of the primary condition, autonomic dysfunction underlies orthostatic hypotension.
Orthostatic hypotension may be a severely disabling condition which can seriously interfere with the quality of life of afflicted subjects. Currently available therapeutic options provide some symptomatic relief in a subset of subjects, but are relatively ineffective and are often accompanied by severe side effects that limit their usefulness. Support garments (tight-fitting leotard) may prove useful in some subjects, but is difficult to don without family or nursing assistance, especially for older subjects. Midodrine, fludrocortisone, methylphenidate, ephedrine, indomethacin and dihydroergotamine are among 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.
The current withdrawal design study will measure the efficacy of droxidopa on symptoms of neurogenic orthostatic hypotension in patients randomized to continued droxidopa treatment versus placebo, following 14 days of double-blind treatment.
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, and Parkinson's disease. There are four stereoisomers of DOPS; however, only the L-threo-enantiomer (droxidopa) is biologically active.
The exact mechanism of action of droxidopa in the treatment of symptomatic NOH has not been precisely defined; however, its NE replenishing properties with concomitant recovery of decreased noradrenergic activity are considered to be of major importance.
Droxidopa has been marketed in Japan since 1989. Data from clinical studies and post-marketing surveillance programs conducted in Japan show that the most commonly reported adverse drug reactions with droxidopa are increased blood pressure, nausea, and headache. In clinical studies, the prevalence and severity of droxidopa adverse effects appear to be similar to those reported by the placebo control arm.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 181
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Droxidopa Droxidopa Double-blind Placebo Placebo Double-blind
- Primary Outcome Measures
Name Time Method Change in Dizziness/ Lightheadedness/ Feeling Faint/ or Feeling Like You Might Blackout (OHSA Item 1) 14 days OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
- Secondary Outcome Measures
Name Time Method Change in Fatigue (OHSA Item 4) 14 days OHSA item 4 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
Change in Weakness (OHSA Item 3) 14 days OHSA item 3 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
Change in Vision (OHSA Item 2) 14 days OHSA item 2 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
Change in Concentration (OHSA Item 5) 14 days OHSA item 5 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
Change in Head/Neck Discomfort (OHSA Item 6) 14 days OHSA item 6 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
Change in Ability to Conduct Activities of Daily Living Score (OHDAS Composite Score) 14 days The OHDAS scale is the average of four items: 1) Standing for a short time; 2) Standing for a long time; 3) Walking for a short time; and 4) Walking for a long time. Each asks the patient to rate their disease impact over the past week. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
Change in Orthostatic Hypotension Symptom Assessment Score (OHSA Composite) 14 days The OHSA scale is the average of six items: 1) Dizziness, lightheadedness, feeling faint or feeling like you might black out; 2) Problems with vision; 3) Weakness; 4) Fatigue; 5) Trouble concentrating; and 6) Head/neck discomfort. Each asks the patient to rate their symptoms over the past week. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
Change in Orthostatic Hypotension Symptom Scores Excluding Dizziness (OHSA Composite Items 2-6) 14 days OHSA composite scale (items 2-6) is the average of five OHSA items: 2) Problems with vision; 3) Weakness; 4) Fatigue; 5) Trouble concentrating; and 6) Head/neck discomfort. Each asks the patient to rate their symptoms over the past week. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
Change in Systolic Blood Pressure (SBP) Measurements 3 Minutes Post Standing; 14 days Change: standing systolic blood pressure at end of study minus standing systolic blood pressure at randomization. In this withdrawal design, a negative score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
Trial Locations
- Locations (54)
University of Maryland
🇺🇸Baltimore, Maryland, United States
The Parkinson's Institute
🇺🇸Sunnyvale, California, United States
Parkinson's Disease & Movment Disorder Center
🇺🇸Boca Raton, Florida, United States
Indiana Medical Research
🇺🇸Elkhart, Indiana, United States
Pacific Neuroscience Medical Group
🇺🇸Oxnard, California, United States
Mayo Jacksonville Florida Department of Neurology
🇺🇸Jacksonville, Florida, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Medical Associates of North Georgia
🇺🇸Canton, Georgia, United States
The Parkinson's and Movement Disorders Institute
🇺🇸Fountain Valley, California, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Southeastern Integrated Medical
🇺🇸Gainesville, Florida, United States
Columbia University
🇺🇸New York, New York, United States
Wake Forest University
🇺🇸Winston Salem, North Carolina, United States
Jacinto Medical Group, PA
🇺🇸Baytown, Texas, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
NYU Medical Center
🇺🇸New York City, New York, United States
Quebec Memory and Motor Skills Disorders Clinic
🇨🇦Quebec, Canada
University of Miami
🇺🇸Miami, Florida, United States
JWM Neurology
🇺🇸Indianapolis, Indiana, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Kansas City Bone and Joint, PA
🇺🇸Overland Park, Kansas, United States
Electrophysiology Associates
🇺🇸Colorado Springs, Colorado, United States
University of Rochester
🇺🇸Rochester, New York, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
The Oregon Clinic
🇺🇸Portland, Oregon, United States
Xenoscience Inc.
🇺🇸Phoenix, Arizona, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
COR Clinical Research, LLC
🇺🇸Oklahoma City, Oklahoma, United States
Parkinson's & Neurodegenerative Disorders Clinic
🇨🇦Ottawa, Ontario, Canada
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Dedicated Clinical Research
🇺🇸Litchfield Park, Arizona, United States
Saint Mary of Nazareth Hospital Center
🇺🇸Chicago, Illinois, United States
North Chicago VA Medical Center
🇺🇸North Chicago, Illinois, United States
New Jersey Neuroscience Institute
🇺🇸Edison, New Jersey, United States
East Texas Medical Center
🇺🇸Tyler, Texas, United States
Scott & White Healthcare - Round Rock
🇺🇸Round Rock, Texas, United States
Austin Hospital
🇦🇺Heidelburg, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Baker Heart Research Institute
🇦🇺Melbourne, Victoria, Australia
Centre for Movement Disorders
🇨🇦Markham, Ontario, Canada
McMaster University
🇨🇦Hamilton, Ontario, Canada
SMBD Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Van der Veer Institute for Parkinson's Disease and Movement Disorders
🇳🇿Christchurch, New Zealand
Auckland Hospital
🇳🇿Grafton Auckland, Private Bag, New Zealand
Washington University Medical Center
🇺🇸St. Louis, Missouri, United States
Kingston Neurological Associates, PC
🇺🇸Kingston, New York, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Scott & White Memorial Hospital & Clinic
🇺🇸Temple, Texas, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
University of Massachusetts Worcester
🇺🇸Worcester, Massachusetts, United States
Henry Ford Health System
🇺🇸Southfield, Michigan, United States
Sun Health Research Institute
🇺🇸Sun City, Arizona, United States
University of South Florida
🇺🇸Tampa, Florida, United States