PPMI 2.0 Clinical -Establishing a Deeply Phenotyped PD Cohort
PPMI 2.0 Clinical -Establishing a Deeply Phenotyped PD Cohort
The Parkinson Progression Marker Initiative 2.0 (PPMI 2.0) is a longitudinal, observational,
 multi-center natural history study to assess progression of clinical features, digital
 outcomes, and imaging, biologic and genetic markers of Parkinson's disease (PD) progression
 in study participants with manifest PD, prodromal PD, and healthy controls

 The overall goal of PPMI 2.0 is to identify markers of disease progression for use in
 clinical trials of therapies to reduce progression of PD disability.
PPMI 2.0 is a broad program, expanding the goals of the original PPMI study (NCT01141023),
 that includes this PPMI 2.0 Clinical protocol, as well as the PPMI 2.0 Remote, PPMI 2.0
 Digital Applications and PPMI 2.0 Online protocols. All participants in PPMI 2.0 will be
 asked to be enrolled in all PPMI 2.0 protocols, but depending on their method of recruitment,
 participants may be enrolled sequentially in varying order, as appropriate. PPMI 2.0
 participants may also be asked to participate in additional PPMI 2.0 companion studies (as
 they are developed), which may only involve a subset of PPMI 2.0 participants based on their
 cohort designation and/or site location.
Inclusion Criteria:

 Parkinson Disease (PD) Subjects:

 -  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 with 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

 -  Woman may not be pregnant, lactating or planning pregnancy during the study.
 ~Including a negative pregnancy test on day of Screening DaTscan imaging test prior to
 injection of DaTscan.

 Healthy Control (HC) Subjects:

 -  Male or female age 30 years or older at Screening visit.

 -  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

 -  Women may not be pregnant, lactating or planning pregnancy during the study. ~
 Includes a negative pregnancy test on day of Screening DaTscan imaging test prior to
 injection of DaTscan™.

 Exclusion Criteria:

 Parkinson Disease (PD) Subjects:

 -  Currently taking levodopa, dopamine agonists, MAO-B inhibitors (e.g., selegiline,
 rasagiline), amantadine or other PD medication.

 -  Has taken levodopa, dopamine agonists, MAO-B inhibitors or amantadine within 60 days
 of Baseline.

 -  Has taken levodopa or dopamine agonists prior to Baseline 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.

 -  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 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 Control (HC) Subjects:

 -  Current or active clinically significant neurological disorder (in the opinion of the
 Investigator).

 -  First degree relative with PD (parent, sibling, child).

 -  Previously obtained MRI scan with evidence of clinically significant neurological
 disorder (in the opinion of the Investigator)

 -  Received any of the follow 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.

 Inclusion Criteria:

 (PD-LRRK2 or GBA) Participants:

 -  Male or female age 30 years or older at Screening visit.

 -  A diagnosis of Parkinson disease for 2 years or less at Screening Visit.

 -  Patients must have a 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.

 -  Confirmation of causative LRRK2 or GBA (willingness to undergo genetic testing as part
 of genetic screening and be informed of genetic testing results, or documentation of
 prior genetic testing results).

 -  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

 -  Woman may not be pregnant, lactating or planning pregnancy during the study.
 ~Including a negative pregnancy test on day of Screening DaTscan imaging test prior to
 injection of DaTscan™.

 Exclusion Criteria:

 PD-LRRK2 or GBA

 -  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.

 Inclusion Criteria:

 PD-SNCA or rate genetic mutation (such as Parkin or Pink 1))

 -  Male or female age 30 years or older at Screening Visit.

 -  Parkinson disease diagnosis at Screening Visit.

 -  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, II or III at Baseline.

 -  Confirmation of causative SNCA or rare genetic mutation (such as Parkin or Pink 1)
 (willingness to undergo genetic testing as part of genetic screening and be informed
 of genetic testing results, or documentation of prior genetic testing results).

 -  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

 -  Woman may not be pregnant, lactating or planning pregnancy during the study.
 ~Including a negative pregnancy test on day of Screening DaTscan imaging test prior to
 injection DaTscan™.

 Exclusion Criteria:

 PD-SNCA or rate genetic mutation (such as Parkin or Pink 1))

 -  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.

 Prodromal Subjects:

 Inclusion Criteria For Screening:

 -  Enrolled in PPMI 2.0 Remote and based on risk criteria, or olfaction, and/or other
 assessments in the PPMI 2.0 Online protocol are eligible for PPMI 2.0 Clinical.

 -  Male or female age 60 years or older (except age 30 years or older for SNCA, or rate
 genetic mutations (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

 -  Woman may not be pregnant, lactating or planning pregnancy during the study.
 ~Including a negative pregnancy test on day of Screening DaTscan imaging test prior to
 injection of DaTscan™.

 Exclusion Criteria : Prodromal

 -  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.