Biomarker Validation Following Sargramostim Treatment in Parkinson's Disease
Parkinson's Disease and ParkinsonismInvestigators will evaluate the safety of a 48 week regimen of Leukine administered as a weight-based dose at 3 ug/kg/ day for 5 days followed by a 2-day holiday. This 48 week long study will extend the prior biomarker evaluations observed in a previous study. Clinical signs and symptoms will be measured by personal well-being, physical, and neurological examinations (UPDRS Parts I, II, III, and IV assessments) and blood tests (CBC with differential, total T cell count, and a comprehensive metabolic sera panel). Leukapheresis will be performed to collect large numbers of immune cells for biomarker testing and immune phenotyping. Additionally, the investigators will determine whether immune deficits of PD are consistent during baseline data collection, and the potential Leukine-induced motor control and mobility improvements will be determined by UPDRS part I, II, III, and IV scores off treatment and on treatment.
External vs Internal-triggered Augmented-reality Visual Cues to Treat Freezing of Gait
Parkinson DiseaseGait Disorders7 morePostural instability, freezing-of-gait (FOG), and falls are among the greatest unmet needs in Parkinson disease (PD). FOG eventually affects more than half of people with PD, and is notoriously difficult to treat pharmacologically or via deep brain stimulation. Visual cues do improve gait freezing, but their efficacy and adoption is limited because they are not practical to use in all real-world situations. There is a need for a cueing technique that is on-demand and discreet - only perceptible to the patient. Fortunately, recent technological advances in augmented-reality (AR) enable such an approach. In this study, state-of-the-art AR glasses will be used to project digital cues that are only visible to the wearer, to determine if they can improve FOG. 36 individuals with PD and FOG will be recruited to perform an obstacle-course gait task under six cue conditions: no cue, conventional cue, constant-on AR, patient-hand-triggered AR (turns on when patient clicks button), patient-eye-triggered AR (turns on when looking down), and examiner-triggered AR. The AR cue is a set of images that appear on the floor at a patient's feet, mimicking floor lines. Gait performance will be captured on video and via body-worn wireless sensors that detect how each limb is moving. The investigators will determine whether individuals are cue-able with conventional visual cues, whether intermittent cues outperform constant-on cues, and whether cues triggered by an examiner outperform cues triggered by patients themselves.
Smoking Cessation With Varenicline in Schizophrenia: Antipsychotic-Induced Neurological Symptoms...
SchizophreniaSchizoaffective Disorder3 moreTo test the feasibility of studying effects of smoking cessation with varenicline on antipsychotic drug-induced neurological side effects, we propose a 12 week pilot study of smoking cessation treatment with varenicline in 10 schizophrenia or schizoaffective disorder patients who are actively smoking and have pre-existing TD while receiving stable doses of antipsychotics. Subjects will be followed after a 2 week baseline period to assess changes in smoking status and neurological symptoms using standardized rating scales. The aim is to examine clinically significant effects on antipsychotic-induced neurological side effects that may warrant further investigation.
Trial of Parkinson's And Zoledronic Acid
Parkinson DiseaseOsteoporosis7 moreThis home-based study is a randomized (1:1) placebo-controlled trial of a single infusion of zoledronic acid-5 mg (ZA) for the prevention of fractures in men and women aged 60 years and older with Parkinson's disease and parkinsonism with at least 2 years of follow-up. A total of 3500 participants will be enrolled and randomized in the United States. Participants, follow-up outcome assessors, and study investigators will be blinded to assigned study treatment. This trial is funded by the National Institute of Aging.
Aim 3 Particle Swarm Optimization PIGD
Parkinson's Disease and ParkinsonismIn Parkinson's disease (PD) patients undergoing standard-of-care Deep Brain Stimulation (DBS) therapy, to compare the effect on Parkinson's symptoms of two different neurostimulator settings designed to differ from each other as much as possible with respect to how much they activate two different neuroanatomical structures: the axonal pathway from Globus Pallidus (GP) to Pedunculopontine Nucleus (PPN), and the axonal pathway from PPN to GP.
Mobility in Atypical Parkinsonism: a Trial of Physiotherapy
Multiple System AtrophyParkinson Variant (Disorder)2 morePatients with atypical parkinsonism often show gait and mobility impairment manifesting in early disease stages. In order to maintain mobility and physical autonomy as long as possible for these patients, we will examine the effect of two types of physiotherapy in patients with multiple system atrophy (MSA), progressive supranuclear gaze palsy (PSP) and idiopathic Parkinson's disease (IPD). The study is divided into an ambulant daily in-patient physiotherapy phase, followed by a home-based training phase. At the beginning and the end of the study, the patients daily activity will be recorded for one week using Physical Activity Monitoring (PAM) sensors. The aim of this double-blind, randomized-controlled study is to determine effective physiotherapy in patients with atypical parkinsonian syndromes in order to maintain mobility for as long as possible.
Efficacy and Safety of Astragalus for Non-motor Symptoms of α-Synucleinopathy
Parkinsonismα-Synucleinopathy is a cluster of neurodegenerative disease with motor and non-motor symptom. However, there is still a lack of research on the treatment for non-motor symptoms of α-synucleinopathy, especially autonomic dysfunctions such as orthostatic hypotension. Efficacy and safety of astragalus for non-motor symptoms of α-synucleinopathy will be assessed by an open-label self-controlled before-and-after study.
Effects of Transcranial Direct Current Stimulation (tDCS) on Motor Function in Schizophrenia Patients...
SchizophreniaPsychosis2 moreThe purposes of this research are to investigate (1) if schizophrenia patients and at-risk individuals present bradykinesia and dyskinesia and (2) if tDCS improves motor performance in schizophrenia patients and at-risk individuals. The first hypothesis is that both schizophrenia patients and at-risk individuals show bradykinesia and dyskinesia, and the motor symptoms are more severe in the former than the latter. The second hypothesis is that tDCS improves motor performance in schizophrenia patients and at-risk cases.
Establishing 18F PMPBB3 (APN 1607) PET Imaging Markers for Diagnosis of Tauopathy Parkinsonism Syndromes...
Tau Distributions in Patients With Tauopathy Using APN-1607 PET ScanParkinson's disease (PD) is one of the most common neurodegenerative disorders. The diagnosis of PD is primarily based on clinical presentations while the pathology stage of a-synuclein containing Lewy body deposition has already advanced. In addition to PD, there is another group of patients presenting with parkinsonism features mixed with other neurodegenerative symptoms. Pathologically, patients with these PD-mimicking parkinsonism syndromes, such as progressive supranuclear palsy (PSP), corticobasal degeneration disorders (CBGD) and frontotemporal dementia (FTD) with/without parkinsonism, have 4 repeat paired helical filament forms of tau protein (4R PHF-tau) aggregations in the neurons. Patients with these tauopathy related parkinsonism-plus syndromes could initially present as PD symptoms but will have a more deliberating disease course and combine with other systems degeneration. These patients are often a substantial diagnostic challenge to clinicians. Therefore, there is an urgent need to develop reliable imaging and biofluid biomarkers for differentiating patients with PD and variable parkinsonism-plus syndromes. Recently, new generation of novel radiotracer 18F-PMPBB3 (APN-1607), which can be labeled with 4R PHF-tau without significant off-target binding, has been successfully developed. Therefore, this study will enroll 150 participants, including 30 healthy controls, 30 PD patients, and 60 patients with different parkinsonism-plus syndromes (including 10 patients with multiple system atrophy, 10 patients with progressive supranuclear palsy, 10 patients with cortical basal syndrome and 30 patients with frontotemporal dementia), and 30 patients with mild cognitive decline (MCI) or Alzheimer's disease (AD). All participants will receive complete neurological examination, 18F-PMPBB3 (APN-1607) PET, brain MRI scans, plasma markers for total/phosphorylated tau, a-synuclein and Ab42/Ab40 and genetic markers covering MAPT、SNCA、LRRK2、GBA and APOE genes. We aim to explore: Whether 18F-PMPBB3 (APN-1607) can differentiate patients with tauopathy (PSP, CBGD, FTD, MCI and AD) and synucleinopathy (PD, MSA). Whether the distribution of tau deposition detected by 18F-PMPBB3 (APN-1607) correlate to disease severity, progression, and prognosis in patients with tauopathy. Whether the loading of tau deposition detected by 18F-PMPBB3 (APN-1607) correlate to plasma levels of total/phosphorylated tau. Determine specific genetic susceptibility sub-groups are more vulnerable to tau deposition detected by 18F-PMPBB3 (APN-1607) in patients with tauopathy. The research results will help to understand the potential of 18F-PMPBB3 (APN-1607) as an imaging biomarker for diagnosis, severity and therapeutic assessment tool for patients with tauopathy.
STEM-PD Open Label Extension (OLE)
Parkinson DiseaseParkinson's Disease and ParkinsonismThis study seeks to establish the safety and efficacy of extended twice daily treatments for treating symptoms associated with PD. Only participants who completed the STEM-PD RCT trial are eligible for the OLE.