The main study objectives include to:a. Use clinical and biological data to estimate the mean rates of change and the variability around the mean of clinical, digital, imaging, biological and genetic outcomes in study participants.b. Confirm…
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Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Key PPMI outcomes will be longitudinal change in clinical (motor and non-motor)
scales (e.g., MDS-UPDRS, MoCA) and PROs and digital outcomes, quantitative
imaging (DAT, SBR, and MRI midbrain melanin), and biologic measures of
synuclein, lysosomal function, and analytes related to neurodegeneration (e.g.,
neurofilament light chain inflammation). Detailed demographic, clinical and
biological data will be collected to test specific hypotheses in subsequent
analyses and other associated protocols. In addition, data quality metrics
including compliance with study procedures, quality metrics related to
biosamples and completeness of data collection will be monitored on an ongoing
basis.
Secondary outcome
Detailed demographic, clinical and biological data will be collected to test
specific hypotheses in subsequent analyses and other associated protocols.
In addition, data quality metrics including compliance with study procedures,
quality metrics related to biosamples and completeness of data collection will
be monitored on an ongoing basis.
Background summary
Parkinson disease (PD) is characterized by an insidious onset and inexorable
but heterogenous progression. Reliable and well-validated biomarkers to monitor
progression would contribute to research into both PD etiology and
therapeutics. Much progress has been made in identifying and assessing PD
biomarkers, and yet no fully validated biomarker or set of biomarkers for PD
are currently available.
During the past decade, the PPMI study has established a longitudinal clinical
and biomarker data resource on approximately 1,500 participants including
cohorts with idiopathic PD, PD with genetic mutations, prodromal participants
and healthy controls (ClinicalTrials.gov NCT01141023). The PPMI Clinical study
is an extension of this initial PPMI study.
Study objective
The main study objectives include to:
a. Use clinical and biological data to estimate the mean rates of change and
the variability around the mean of clinical, digital, imaging, biological and
genetic outcomes in study participants.
b. Confirm existing and identify novel clinical, digital, imaging, biologic and
genetic PD progression markers
c. Evaluate the probability of phenoconversion to PD for individuals with
prodromal PD.
For these objectives, the study will make use of specific subgroups, as defined
within the PPMI Clinical cohort:
- participants with a PD diagnosis (including patients with a LRRK2, GBA, SNCA
or rare genetic mutation (such as Parkin o Pink1);
- prodromal participants (including individuals with RBD, olfactory loss, a
LRRK2, GBA, SNCA or rare genetic variants (such as Parkin or Pink1) and/ or
other risk factors for PD with and without DAT deficit); and
- healthy controls.
Study design
PPMI Clinical is a longitudinal, observational, multi-center natural history
study to assess progression of clinical features, digital outcomes, and
imaging, biologic and genetic markers of PD progression in study participants
with PD diagnosis (including patients with a LRRK2, GBA, SNCA or rare genetic
variants and individuals with prodromal Parkinson disease (including
individuals with RBD, olfactory loss, LRRK2, GBA, SNCA or rare genetic variants
(such as Parkin or Pink1) and/or other risk factors for PD with and without DAT
deficit and healthy controls.
The Radboudumc, as a participating center, will include participants diagnosed
with PD, without a genetic variant and individuals with prodromal Parkinson's
disease.
All participants will be comprehensively assessed for a minimum of 5 years.
Participants will undergo clinical (motor, neuropsychiatric and cognitive) and
imaging assessments, and will donate biosamples including blood, urine, and
cerebral spinal fluid (CSF) and skin biopsy.
Study burden and risks
For the baseline visit, participants come to the study site at Radboudumc in
Nijmegen, which will take approximately 8 hours. After baseline, participants
will be evaluated in clinic every 6 months for the first two years. Annual
visits are anticipated to take about 6-8 hours (could occur over more than one
day), while the 6-month in clinic visits will take about 2-4 hours.
After two years, all participants will continue to be evaluated every 6 months
remotely and annually in the clinic, for up to 5 years of longitudinal follow
up visits. Options for Remote 6-month visits include virtual visits by video
link or telemedicine, or phone/audio only. The remote 6-month visits will take
about 1-2 hours.
All study assessments are routine exams done in standard clinical practice and
are generally well tolerated.
Because data collection is not performed for immediate diagnostic or
therapeutic purposes, there will be no direct benefits for the subjects
enrolled in this study. Patients will indirectly benefit from the study, as
their data contribute to gain novel etiological insights for improvement of
existing treatments, including more personalized disease management, and the
development of new therapeutic approaches.
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Listed location countries
Age
Inclusion criteria
Patients
- Male or female age 30 years or older at Screening Visit.
- A diagnosis of Parkinson disease for 2 years or less at Screening Visit.
- Not expected to require PD medication within at least 6 months from
Baseline.
- Patients must have at least two of the following: resting tremor,
bradykinesia, rigidity (must have either resting tremor or bradykinesia); OR
either asymmetric resting tremor or asymmetric bradykinesia.
- Hoehn and Yahr stage I or II at Baseline.
- Individuals taking any of the following drugs: alpha methyldopa,
methylphenidate, amphetamine derivatives or modafinil, must be willing and
medically able to hold the medication for at least 5 half -lives before DaTscan
imaging.
- Confirmation that participant is eligible based on Screening DaTscan imaging.
- Able to provide informed consent.
- Either is male, or is female and meets additional criteria below, as
applicable:
- Female of childbearing potential who is not pregnant, lactating or planning
pregnancy during the study and has a negative pregnancy test on day of
Screening DaTscan imaging test prior to injection of DaTscanTM.
Health controls for prodromal cohort
For Screening:
- Confirmation that participant is eligible based on centrally determined
predictive criteria, i.e., meeting one of the following criteria:
- Generalized risk, i.e., first degree biologic relative (parents, siblings)
with PD; or
- Known risk of PD including RBD; or
- Known genetic variants associated with PD risk, i.e., LRRK2, GBA, SNCA or
rare genetic variants (such as Parkin or Pink1).
In addition, the participant needs a positive indication of Olfactory loss with
the University of Pennsylvania Smell Identification Test (UPSIT), performed
during the Screening visit, prior to DaTscan.
- Male or female.
- Age 60 years or older (except age 30 years or older for SNCA, or rare genetic
variants (such as Parkin or Pink1) participants).
- Individuals taking any of the following drugs: alpha methyldopa,
methylphenidate, amphetamine derivatives or modafinil, must be willing and
medically able to hold the medication for at least 5 half-lives before DaTscan
imaging.
- Able to provide informed consent.
For ST Direct participation (as recruitment strategy for the prodromal cohort):
- Male or female
- Age 60 years or older
- No diagnosis of Parkinson's disease
- Living in the Netherlands
Additional criteria, as applicable:
- Female of childbearing potential who is not pregnant, lactating, or planning
pregnancy during the study and has a negative pregnancy test on day of
Screening DaTscan imaging test prior to injection of DaTscanTM.
For continuation to Baseline visit and ongoing follow-up:
- Confirmation that participant is eligible based on *Screening DaTscan
imaging.
Exclusion criteria
Patients:
-Currently taking levodopa, dopamine agonists, MAO-B inhibitors (e.g.,
selegiline, rasagiline), amantadine or another PD medication, except for
low-dose treatment of restless leg syndrome.
-Has taken levodopa, dopamine agonists, MAO-B inhibitors or amantadine within
60 days of Baseline visit, except for low-dose treatment of restless leg
syndrome.
- Has taken levodopa or dopamine agonists prior to Baseline visit for more than
a total of 90 days.
-Atypical PD syndromes due to either drugs (e.g., metoclopramide, flunarizine,
neuroleptics) or metabolic disorders (e.g., Wilson*s disease), encephalitis, or
degenerative diseases (e.g., progressive supranuclear palsy).
-A clinical diagnosis of dementia as determined by the investigator, at
screening.
-Previously obtained MRI scan with evidence of clinically significant
neurological disorder (in the opinion of the Investigator).
-Received any of the following drugs: dopamine receptor blockers
(neuroleptics), metoclopramide and reserpine within 6 months of Screening visit.
-Current treatment with anticoagulants (e.g., coumadin, heparin, oral thrombin
inhibitors) that might preclude safe completion of the lumbar puncture.
-Condition that precludes the safe performance of routine lumbar puncture, such
as prohibitive lumbar spinal disease, bleeding diathesis, or clinically
significant coagulopathy or thrombocytopenia.
-Any other medical or psychiatric condition or lab abnormality, which in the
opinion of the investigator might preclude participation.
Healthy controls for prodromal cohort:
- Clinical diagnosis of PD, other parkinsonism, or dementia.
- Received any of the following drugs: dopamine receptor blockers
(neuroleptics), metoclopramide and reserpine within 6 months of Screening Visit.
- Current treatment with anticoagulants (e.g. coumadin, heparin) that might
preclude safe completion of the lumbar puncture.
- Condition that precludes the safe performance of routine lumbar puncture,
such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically
significant coagulopathy or thrombocytopenia.
- Any other medical or psychiatric condition or lab abnormality, which in the
opinion of the investigator might preclude participation.
- Implants (such as dentals) or metal splinters in upper body that are not
allowed to undergo a MRI scan.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04477785 |
| CCMO | NL77098.091.21 |