| Eligibility |
7.1 Healthy Controls (HC) Note: Active Healthy controls previously enrolled in PPMI do not
require re-assessment of eligibility criteria listed below for enrollment in PPMI Clinical.
Active participants do need to be able to provide informed consent for PPMI Clinical
participation (includes use of a designated research proxy).
7.1.1 Inclusion Criteria (HC)
1. Male or female age 57 years or older at Screening visit.
2. 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 SPECT imaging.
3. Confirmation that participant is eligible based on Screening SPECT imaging.
4. Able to provide informed consent.
5. 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
SPECT imaging test prior to injection of DaTscanTM.
7.1.2 Exclusion Criteria (HC)
1. First degree relative with PD (i.e., biologic parent, sibling, child).
2. Current or active clinically significant neurological disorder (in the opinion of the
Investigator).
3. Previously obtained MRI scan with evidence of clinically significant neurological
disorder (in the opinion of the Investigator).
4. Received any of the following drugs: dopamine receptor blockers (neuroleptics),
metoclopramide and reserpine within 6 months of Screening visit.
5. Current treatment with anticoagulants (e.g., coumadin, heparin, oral thrombin
inhibitors) that might preclude safe completion of the lumbar puncture.
6. Condition that precludes the safe performance of routine lumbar puncture, such as
prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant
coagulopathy or thrombocytopenia.
7. Any other medical or psychiatric condition or lab abnormality, which in the opinion of
the investigator might preclude participation.
8. Any other reason that, in the opinion of the investigator, would render the
participant unsuitable for study enrollment.
7.2 Parkinson's Disease (PD) Note: Active PD participants previously enrolled in PPMI do
not require re-assessment of eligibility criteria listed below for enrollment in PPMI
Clinical. Active participants do need to be able to provide informed consent for PPMI
Clinical participation (includes use of a designated research proxy).
7.2.1 Inclusion Criteria (PD)
1. Male or female age 30 years or older at Screening Visit.
2. A diagnosis of Parkinson's disease for 2 years or less at Screening Visit.
3. Not expected to require PD medication within at least 6 months from Baseline.
4. 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.
5. Hoehn and Yahr stage I or II at Baseline.
6. 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 SPECT imaging.
7. Confirmation that participant is eligible based on Screening SPECT imaging.
8. Able to provide informed consent.
9. 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
SPECT imaging test prior to injection of DaTscanTM.
7.2.2 Exclusion Criteria (PD)
1. Currently taking levodopa, dopamine agonists, MAO-B inhibitors, amantadine or another
PD medication, except for low-dose treatment of restless leg syndrome (with permission
of medical monitor).
2. Has taken levodopa, dopamine agonists, MAO-B inhibitors or amantadine within 60 days
of Baseline visit.
3. Has taken levodopa or dopamine agonists prior to Baseline visit for more than a total
of 90 days.
4. 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).
5. A clinical diagnosis of dementia as determined by the investigator.
6. Previously obtained MRI scan with evidence of clinically significant neurological
disorder (in the opinion of the Investigator).
7. Received any of the following drugs: dopamine receptor blockers (neuroleptics),
metoclopramide and reserpine within 6 months of Screening visit.
8. Current treatment with anticoagulants (e.g., coumadin, heparin, oral thrombin
inhibitors) that might preclude safe completion of the lumbar puncture.
9. Condition that precludes the safe performance of routine lumbar puncture, such as
prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant
coagulopathy or thrombocytopenia.
10. Any other medical or psychiatric condition or lab abnormality, which in the opinion of
the investigator might preclude participation.
11. Any other reason that, in the opinion of the investigator, would render the
participant unsuitable for study enrollment.
7.3 Parkinson's Disease (PD) with LRRK2 or GBA variant Note: Active PD participants
previously enrolled in PPMI do not require re-assessment of eligibility criteria listed
below for enrollment in PPMI Clinical. Active participants do need to be able to provide
informed consent for PPMI Clinical participation (includes use of a designated research
proxy).
7.3.1 Inclusion Criteria (PD ¬- LRRK2 or GBA)
1. Male or female age 30 years or older at Screening Visit.
2. A diagnosis of Parkinson's disease for 2 years or less at Screening Visit.
3. 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.
4. Hoehn and Yahr stage I or II at Baseline.
5. Confirmation of causative LRRK2 or GBA (willingness to undergo genetic testing as part
of genetic screening and be informed of genetic testing results, or approved
documentation of prior genetic testing results).
6. 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 SPECT imaging.
7. Confirmation that participant is eligible based on Screening SPECT imaging.
8. Able to provide informed consent.
9. 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
SPECT imaging test prior to injection of DaTscanTM.
7.3.2 Exclusion Criteria (PD - LRRK2 or GBA)
1. Received any of the following drugs: dopamine receptor blockers (neuroleptics),
metoclopramide and reserpine within 6 months of Screening visit.
2. Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude
safe completion of the lumbar puncture.
3. Condition that precludes the safe performance of routine lumbar puncture, such as
prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant
coagulopathy or thrombocytopenia.
4. Any other medical or psychiatric condition or lab abnormality, which in the opinion of
the investigator might preclude participation.
5. Any other reason that, in the opinion of the investigator, would render the
participant unsuitable for study enrollment.
7.4 Parkinson's Disease (PD) with SNCA or rare genetic variant Note: Active PD participants
previously enrolled in PPMI do not require re-assessment of eligibility criteria listed
below for enrollment in PPMI clinical. Active participants do need to be able to provide
informed consent for PPMI Clinical participation (includes use of a designated research
proxy).
7.4.1 Inclusion Criteria (PD - SNCA or rare genetic variant (such as Parkin or Pink1))
1. Male or female age 30 years or older at Screening Visit.
2. Parkinson's disease diagnosis at Screening Visit.
3. 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.
4. Hoehn and Yahr stage I, II, or III at Baseline.
5. Confirmation of causative SNCA or rare genetic variant (such as Parkin or Pink1)
(willingness to undergo genetic testing as part of genetic screening and be informed
of genetic testing results, or approved documentation of prior genetic testing
results).
6. 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 SPECT imaging.
7. Confirmation that participant is eligible based on Screening SPECT imaging.
8. Able to provide informed consent.
9. 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
SPECT imaging test prior to injection of DaTscanTM.
7.4.2 Exclusion Criteria (PD - SNCA or rare genetic variant (such as Parkin or Pink1))
1. Received any of the following drugs: dopamine receptor blockers (neuroleptics),
metoclopramide and reserpine within 6 months of Screening visit.
2. Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude
safe completion of the lumbar puncture.
3. Condition that precludes the safe performance of routine lumbar puncture, such as
prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant
coagulopathy or thrombocytopenia.
4. Any other medical or psychiatric condition or lab abnormality, which in the opinion of
the investigator might preclude participation.
5. Any other reason that, in the opinion of the investigator, would render the
participant unsuitable for study enrollment.
7.5 Prodromal Note: Active Prodromal participants previously enrolled in PPMI do not
require re-assessment of eligibility criteria listed below for enrollment in PPMI Clinical.
Active participants do need to be able to provide informed consent for PPMI Clinical
participation (includes use of a designated research proxy).
The specific predictive eligibility criteria for participants recruited through PPMI Remote
to advance to PPMI Clinical will be iteratively optimized based on data collected from
these studies.
7.5.1 Inclusion criteria (Prodromal)
For Screening:
1. Confirmation that participant is eligible based on centrally determined predictive
criteria including the University of Pennsylvania Smell Identification Test (UPSIT).
- For participants in PPMI Remote, referral to the clinical site confirms
predictive eligibility.
- For participants identified by the clinical site, predictive criteria are based
on generalized risk such as first degree biologic relative, known risk of PD
including RBD, or known genetic variants associated with PD risk.
Additionally, confirmation of UPSIT eligibility during the Screening visit prior to
SPECT Imaging.
2. 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).
3. 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 SPECT imaging.
4. Able to provide informed consent.
5. 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 SPECT
imaging test prior to injection of DaTscanTM.
For continuation to Baseline visit and ongoing follow-up:
6. Confirmation that participant is eligible based on *Screening SPECT imaging.
- Screening SPECT Imaging eligibility:
Based on the results of the SPECT imaging test, Prodromal participants eligible to continue
their participation in PPMI Clinical will be asked to return for their PPMI Clinical
baseline visit. Neither the participant nor the site investigator will be made aware of the
participant's DAT status during the study.
- It is anticipated that approximately 6,000 participants will complete a screening
visit to undergo DAT imaging. Approximately 2,000 participants will be eligible to
continue their participation in PPMI Clinical (those not eligible to proceed will
remain in PPMI Remote, as applicable).
- All participants with DAT deficit will be eligible to continue their participation in
PPMI Clinical. It is estimated that about 75% of eligible participants will have a DAT
deficit (defined by a hybrid of visual assessment and quantitative striatal specific
binding analysis).
- Some participants without DAT deficit will also be eligible to continue their
participation in PPMI Clinical. These participants will be chosen based on DAT binding
that is reduced from age expected but it not outside the normal range and/or from
individuals with high-risk of PD including RBD, LRRK2, GBA, SNCA, or rare genetic
variants (such as Parkin or Pink1) that do not demonstrate DAT deficit. It is
estimated that about 25% of eligible participants will not have a DAT deficit.
- It is anticipated that approximately 30% of the PPMI Clinical prodromal participants
with DAT deficit will phenoconvert to motor parkinsonism during a 3 to 5-year
follow-up.
7.5.2 Exclusion Criteria (Prodromal)
1. Clinical diagnosis of PD at screening, other parkinsonism, or dementia.
2. Received any of the following drugs: dopamine receptor blockers (neuroleptics),
metoclopramide and reserpine within 6 months of Baseline Visit.
3. Current treatment with anticoagulants (e.g. coumadin, heparin) that might preclude
safe completion of the lumbar puncture.
4. Condition that precludes the safe performance of routine lumbar puncture, such as
prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant
coagulopathy or thrombocytopenia.
5. Any other medical or psychiatric condition or lab abnormality, which in the opinion of
the investigator might preclude participation.
6. Currently taking levodopa, dopamine agonists, MAO-B inhibitors, amantadine or another
PD medication, except for low-dose treatment of restless leg syndrome (with permission
of medical monitor).
7. 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 (with
permission of medical monitor).
8. Any other reason that, in the opinion of the investigator, would render the
participant unsuitable for study enrollment.
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