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PPMI 2.0 Clinical -Establishing a Deeply Phenotyped PD Cohort (PPMI)

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ClinicalTrials.gov Identifier: NCT04477785
Recruitment Status : Recruiting
First Posted : July 20, 2020
Last Update Posted : August 7, 2020
Sponsor:
Collaborator:
Institute for Neurodegenerative Disorders
Information provided by (Responsible Party):
Ken Marek, MD, Institute for Neurodegenerative Disorders

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
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.

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Study Type : Observational
Estimated 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 : July 1, 2020
Estimated Primary Completion Date : December 2033
Estimated Study Completion Date : December 2033

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. Establish standardized protocols for acquisition, transfer & analysis of clinical, digital, imaging, biologic and genetic data that can be used in the PD research community. [ Time Frame: Baseline to 156 months ]
    This protocol will build on the existing PPMI infrastructure

  2. Comprehensive and uniformly acquired dataset [ Time Frame: 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)

  3. Comparison between Rates of Change [ Time Frame: 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.

  4. Prevalence of measures of clinical, imaging and biomic outcomes in various subsets [ Time Frame: 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.

  5. Establish the probability of phenoconversion to PD [ Time Frame: 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).


Biospecimen Retention:   Samples With DNA
Blood will be obtained for the extraction of DNA to conduct sequencing and genomic analysis. These maybe collected in a fasted state.


Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
In PPMI 2.0 Clinical up to 4,500 participants will be enrolled and followed longitudinally from approximately 40-50 international clinical sites across a variety of cohorts, including healthy controls, Parkinson disease, PD manifesting gene carriers, and Prodromal (those at risk for developing PD).
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04477785


Contacts
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Contact: Cari Rainville, BS 2032159611 crainville@indd.org

Locations
Show Show 48 study locations
Sponsors and Collaborators
Michael J. Fox Foundation for Parkinson's Research
Institute for Neurodegenerative Disorders
Investigators
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Principal Investigator: Kenneth L Marek, MD Institute for Neurodegenerative Disorders
Principal Investigator: Caroline Tanner, MD, PhD University of California, San Francisco
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Responsible Party: Ken Marek, MD, Protocol Co- Principal Investigator, Institute for Neurodegenerative Disorders
ClinicalTrials.gov Identifier: NCT04477785    
Other Study ID Numbers: PPMI-002
First Posted: July 20, 2020    Key Record Dates
Last Update Posted: August 7, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ken Marek, MD, Institute for Neurodegenerative Disorders:
Parkinson
Bio-markers
Neurodegenerative disorder
Imaging
Prodromal
Genetics
At Risk
Loss of Smell
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases