PPMI 2.0 Clinical -Establishing a Deeply Phenotyped PD Cohort

Sponsor

Michael J. Fox Foundation for Parkinson's Research (Other)

Overall Status

Recruiting

CT.gov ID

NCT04477785

Collaborator

Institute for Neurodegenerative Disorders (Other)

4,500

Enrollment

Locations

161

Anticipated Duration (Months)

88.2

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease

Detailed Description

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

4500 participants

Observational Model:

Case-Control

Time Perspective:

Other

Official Title:

The Parkinson's Progression Markers Initiative (PPMI) 2.0 Clinical -Establishing a Deeply Phenotyped PD Cohort

Actual Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Dec 1, 2033

Anticipated Study Completion Date :

Dec 1, 2033

Arms and Interventions

Arm	Intervention/Treatment
Clinical Observation Up to 4500 participants will be followed clinically once identified, over the course of 5-8 years.

Outcome Measures

Primary Outcome Measures

Establish standardized protocols for acquisition, transfer & analysis of clinical, digital, imaging, biologic and genetic data that can be used in the PD research community. [Baseline to 156 months]
This protocol will build on the existing PPMI infrastructure
Comprehensive and uniformly acquired dataset [Baseline to 156 months]
Develop a comprehensive and uniformly acquired clinical, digital and imaging dataset and repository of biological and genetic samples that would be available to the PD research community to test hypotheses of the underlying molecular pathobiology of PD, enable modeling of PD progression to identify clinical and/or data driven PD progression sub-sets, and inform studies testing PD therapeutics (for examples, clinical trials targeting synuclein, LRRK2, GBA as well as other targets)
Comparison between Rates of Change [Study intervals ranging from 3 months to 156 months]
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 with PD diagnosis (including patients with a LRRK2, GBA, SNCA or rare genetic mutations (such as Parkin or Pink1) and individuals with prodromal Parkinson disease (including individuals with RBD, olfactory loss, LRRK2, GBA, SNCA or rare genetic mutations (such as Parkin or Pink1) and/or other risk factors for PD with and without DAT deficit and in healthy participants.
Prevalence of measures of clinical, imaging and biomic outcomes in various subsets [study intervals ranging from baseline to 156 months.]
Confirm existing and identify novel clinical, digital, imaging, biologic and genetic PD progression markers to identify quantitative individual measures or combinations of measures that demonstrate optimum interval change in study participants with PD diagnosis (including patients with a LRRK2, GBA, SNCA or rare genetic mutations (such as Parkin or Pink1)) and individuals with prodromal Parkinson disease (including individuals with RBD, olfactory loss, a LRRK2, GBA, SNCA or rare genetic mutations (such as Parkin or Pink1) and/or other risk factors for PD with and without DAT deficit in comparison to healthy controls or in sub-sets of study participants with PD diagnosis or prodromal PD defined by baseline assessments, progression milestones and/or rate of clinical, digital, imaging, biologic and genetic change, or other measures.
Establish the probability of phenoconversion to PD [study intervals ranging from baseline to 156 months.]
Evaluate the probability of phenoconversion to PD for individuals with prodromal PD enrolled in the prodromal cohorts (including individuals with RBD, olfactory loss, a LRRK2, GBA, SNCA or rare genetic mutations (such as Parkin or Pink1) and/ or other risk factors for PD with and without DAT deficit).

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Barrow Neurological Institute	Phoenix	Arizona	United States	85013
3	Mayo Foundation for Medical Education and Research	Scottsdale	Arizona	United States	85259
4	Banner Research Institute	Sun City	Arizona	United States	85351
5	University of California San Diego	La Jolla	California	United States	92093-0948
6	Keck School of Medicine of USC	Los Angeles	California	United States	90033
7	University of California, San Francisco	San Francisco	California	United States	94115
8	University of Colorado Anschutz Medical Campus	Aurora	Colorado	United States	80045
9	Institute For Neurodegenerative Disorders	New Haven	Connecticut	United States	06510
10	Parkinson's Disease& Movement Disorder Center of Boca Raton	Boca Raton	Florida	United States	33486
11	University of Florida	Gainesville	Florida	United States	32608
12	University of South Florida	Tampa	Florida	United States	33606
13	Emory University School of Medicine	Atlanta	Georgia	United States	30329
14	Northwestern University	Chicago	Illinois	United States	60611
15	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
16	Johns Hopkins University	Baltimore	Maryland	United States	21287
17	Boston University	Boston	Massachusetts	United States	02118
18	Massachusetts General Hospital	Boston	Massachusetts	United States	02446
19	University of Michigan	Ann Arbor	Michigan	United States	48109
20	Cleveland Clinic Lou Ruvo Center for Brain Health	Las Vegas	Nevada	United States	89106
21	Beth Israel Medical Center	New York	New York	United States	10003
22	NYU Langone Health	New York	New York	United States	10017
23	Columbia University Medical Center	New York	New York	United States	10032
24	University of Rochester	Rochester	New York	United States	14620
25	University of Cincinnati/Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45219
26	Cleveland Clinic	Cleveland	Ohio	United States	44195
27	Oregon Health &Science University	Portland	Oregon	United States	97239
28	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19107
29	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
30	Baylor College of Medicine	Houston	Texas	United States	77030
31	Univ of Washington and VA Puget Sound Health Care System	Seattle	Washington	United States	98104
32	Innsbruck Medical University	Innsbruck		Austria	6020
33	The Ottawa Hospital - Civic Campus	Ottawa	Ontario	Canada	K1Y 4E9
34	Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8
35	McGill University	Montréal	Quebec	Canada	H3A2B4
36	Hospital Pitie-Salpetriere	Paris		France	75013
37	Philipps-University of Marburg	Hessen		Germany	35043
38	Paracelsus-Elena Klinik	Kassel		Germany	34128
39	University of Luebeck	Luebeck		Germany	23562
40	University of Tuebingen	Tuebingen		Germany	72076
41	Foundation for Biomedical Research of the Academy of Athens	Athens		Greece	11523
42	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
43	University of Salerno	Salerno		Italy	84131
44	Radboud University	Nijmegen	Gelderland	Netherlands	6525 GC
45	Lagos College of Medicine, University of Lagos	Lagos		Nigeria	121010
46	St. Olavs Hospital	Trondheim		Norway	7006
47	Hospital Clinic de Barcelona	Barcelona		Spain	08036
48	Hospital Donostia	San Sebastian		Spain	20014
49	Newcastle University	Newcastle Upon Tyne	Tyne And Wear	United Kingdom	NE45PL
50	Imperial College London	London		United Kingdom	W12 0NN
51	John Radcliffe Hospital Oxford and Oxford University	Oxford		United Kingdom	Oxford, OX3 9DU

Sponsors and Collaborators

Michael J. Fox Foundation for Parkinson's Research
Institute for Neurodegenerative Disorders

Investigators

Principal Investigator: Kenneth L Marek, MD, Institute for Neurodegenerative Disorders
Principal Investigator: Caroline Tanner, MD, PhD, University of California, San Francisco