June 27, 2016
Summary
This
research study is being done to determine whether treatment with L-
Dihydroxyphenylserine (L-DOPS) versus placebo (an inactive substance that looks
like study drug) in addition to other Parkinson Disease (PD) drugs will improve
balance, walking, and reduce risk of falls and/or severity of falls in PD
subjects. The study is also being done to determine the effectiveness, safety,
and tolerability of L-DOPS, and whether it will decrease Freezing of Gait
(FOG), improve apathy (generalized disinterest) or show a relationship between
apathy and slowed movement and fall risk.
Description
Among
the top three priorities presented to the National Institute of Neurological
Disorders and Stroke (NINDS) Council 22 as final recommendations of critical
needs for advancing Parkinson Disease (PD) research in 2014 is to develop
effective treatments for dopa-resistant features of PD. These features include
symptoms such as gait and balance problems, and freezing of gait leading to
falls. In order for these goals to be realized, dysfunctional motor patterns in
patients with gait and balance problems need to be accurately defined and
assessed using body-fixed sensors and other newer computation technology to
enhance sensitivity and specificity of measurement to facilitate long-term
follow-up. The proposed research will meet the challenge of determining
appropriate intervention (L-DOPS) for dopa-resistant features of PD in
improving gait and posture using innovative quantitative analyses derived from
body-worn sensors. Injuries associated with fall incidences continue to pose a
significant burden to persons with Parkinson's disease (PD) both in terms of
human suffering and economic losses. Annual fall incidence rates range from
50-70% of patients with PD. Recurrent falls especially, are a major cause of
disability in PD.
The resulting loss of independence and treatment costs add
substantially to the healthcare expenditures in PD which was estimated to be
$27 billion annually2. This number may rise substantially in the coming decades
as the entire US population ages. Any intervention that is cost effective at
reducing fall risk could have important benefits for patients and families, and
for the entire healthcare system. In this study, we will determine whether
treatment with L- Dihydroxyphenylserine (L-DOPS, Northera) in addition to
dopaminergic drugs will improve postural stability and activity of daily
living, and reduce fall risk and/or severity of falls in PD patients.Falls,
early in PD (within 5 years of diagnosis) probably arise from slowed
locomotion. Slowed locomotion is corrected by dopaminergic drugs, hence falls
early in PD are decreased by such drugs. Later in PD (5 or years after
diagnosis) falls, recurrent falls, occur despite such drugs. There is evidence
that falls late in PD occur because of impaired postural stability which does
not respond to dopaminergic drugs or may be made worse by such drugs.
A single
fall, although serious, may be only partly related or even unrelated to PD.
"Serious fall" is defined as: all four limbs hit the ground, the
skull hits the ground, or there is soft tissue or bone injury. However, some
people with PD fall repeatedly. In such patients the role of impaired postural
stability was stressed. Although the mechanisms underlying impaired postural
stability are not well-known in patients with PD, attention is focused on the
noradrenergic system. L-DOPS, a drug that enhances norepinephrine levels in the
peripheral and central nervous systems, has been shown to moderate orthostatic
hypotension, and often improve some PD symptoms.
There is evidence that
mechanisms related to norepinephrine centers in the basal forebrain and the
locus ceruleus play a role in maintaining postural stability in activities of
daily living. They may play a role in preventing or ameliorating falls and
freezing of gait. FOG is a major problem in patients with PD who fall. There is
evidence that L-DOPS, by improving FOG, decreases risk of falls. Additionally,
evidence indicates that L-DOPS decreases falls independent of improving FOG.
Apathy, a major and disabling non-motor symptom of PD, may be related to
decreased central norepinephrine levels. Apathy may be associated with slowed
movements and slowed movements may contribute to falls. There is evidence that
L-DOPS, by increasing central norepinephrine, may improve apathy and this may
result in a decreased risk of falls.
Study Design
Allocation:
Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model:
Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary
Purpose: Treatment
Conditions
Parkinson
Disease
Intervention
L-DOPS,
Placebo
Location
Barrow
Neurological Institute/St. Joseph's Hospital and Medical Center
Phoenix
Arizona
United
States
85013
Status
Recruiting
http://www.bioportfolio.com/resources/trial/160761/Effect-of-L-Dihydoxyphenylserine-on-Locomotion-Postural-Stability-and-Fall-Risk-Reduction.html
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