The Parkinson*s Progression Markers Initiative (PPMI) Clinical - Establishing a Deeply Phenotyped PD Cohort

Recruiting

Conditions: Parkinson's disease
10028037

Registration Number: NL-OMON56457

Lead Sponsor: Michael J Fox Foundation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 75

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.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Key PPMI outcomes will be longitudinal change in clinical (motor and non-motor)<br /><br>scales (e.g., MDS-UPDRS, MoCA) and PROs and digital outcomes, quantitative<br /><br>imaging (DAT, SBR, and MRI midbrain melanin), and biologic measures of<br /><br>synuclein, lysosomal function, and analytes related to neurodegeneration (e.g.,<br /><br>neurofilament light chain inflammation). Detailed demographic, clinical and<br /><br>biological data will be collected to test specific hypotheses in subsequent<br /><br>analyses and other associated protocols. In addition, data quality metrics<br /><br>including compliance with study procedures, quality metrics related to<br /><br>biosamples and completeness of data collection will be monitored on an ongoing<br /><br>basis.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Detailed demographic, clinical and biological data will be collected to test<br /><br>specific hypotheses in subsequent analyses and other associated protocols.<br /><br><br /><br>In addition, data quality metrics including compliance with study procedures,<br /><br>quality metrics related to biosamples and completeness of data collection will<br /><br>be monitored on an ongoing basis.</p><br>