Effect of L-Dihydoxyphenylserine on Locomotion, Postural Stability, and Fall Risk Reduction in Parkinson Disease
Status: | Active, not recruiting |
---|---|
Conditions: | Parkinsons Disease |
Therapuetic Areas: | Neurology |
Healthy: | No |
Age Range: | 30 - 83 |
Updated: | 2/17/2019 |
Start Date: | May 2016 |
End Date: | June 2019 |
Effect of L-Dihydoxyphenylserine (L-DOPS, Northera) a Central and Peripheral Norepinephrine Agent on Locomotion, Postural Stability (Balance), and Fall Risk Reduction in Parkinson Disease (PD)
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.
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.
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.
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.
Inclusion Criteria:
- Subject has voluntarily signed and dated an informed consent form (ICF) prior to any
participation in the study.
- Hoehn and Yahr Stage II, III, IV in an "on" state.
- Fell more than twice in past year.
- Montreal Cognitive Assessment (MOCA) score ≥ 24.
- Stable dose of levodopa, dopamine agonist, amantadine, and/or monoamine oxidase B
inhibitor, i.e. unchanged for 3 months.
- Subject is ambulatory and able to walk ≥ 10 meters with/without the use of an
assistive device.
Exclusion Criteria:
- Patients with atypical Parkinson disorders that result in a high number of falls.These
disorders include: Progressive Supranuclear Palsy (PSP), Multiple System Atrophy
(MSA), Primary Freezing of Gait (PFG), and Corticobasal Degeneration.
- Patients with dementia MOCA ≤ 23.
- Patients with symptomatic Orthostatic Hypotension being treated with midodrine,
fludrocortisone or L-DOPS.
- Patients with uncontrolled hypertension.
- Patients with known allergies to L-DOPS or its excipients.
- Patients with major orthopedic problems of their hips or knees, and patients who need
hip or knee replacements.
- Patient with schizophrenia, a schizo-affective disorder, or a bipolar disorder.
- Patients with hallucinations, psychoses, or delusions.
- Patients with a history of recent stroke or myocardial infarction.
We found this trial at
1
site
Phoenix, Arizona 85013
Principal Investigator: Abraham Leiberman, MD
Phone: 602-406-8134
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