PPMI
PPMI Study Overview
Launched in 2010, the Parkinson’s Progression Markers Initiative (PPMI) is a longitudinal observational study of more than 1,500 participants contributing comprehensive clinical and imaging data and biological samples at 33 clinical sites around the world. Sponsored by The Michael J. Fox Foundation and supported by a number of industry partners, PPMI follows participants for five to 13 years. The study has built a robust database and biorepository, which it makes available to the research community to further biomarker discovery and validation and therapeutic development.
Total Participants (Cohort records that met the AMP PD minimum clinical data criteria):
1,943
AMP PD Designation:
Data from the PPMI cohort is designated with the prefix “PP” in the AMP PD Portal. PPMI data in the AMP PD portal includes: Demographics, family history, medication history, MDS-UPDRS, MoCA, WGS, blood transcriptomics
Additional Study Information:
PPMI Study Goals and Objectives
The primary objective of this study is to identify clinical, imaging and biologic markers of PD progression for use in clinical trials of disease-modifying therapies.
The specific aims to accomplish the primary objective are:
Develop a comprehensive and uniformly acquired clinical and imaging dataset and biological samples that can be used to estimate the mean rates of change and the variability around the mean of clinical, imaging and biomic outcomes in early PD patients, prodromal PD subjects, and PD subjects with a LRKK2, GBA or SNCA mutation. Investigate existing and identify novel clinical, imaging, and biomic Parkinson disease progression markers to identify quantitative individual measures or combination of measures that demonstrate optimum interval change in PD patients in comparison to healthy controls, SWEDD subjects, Prodromal subjects, PD subjects with a LRRK2, GBA or SNCA mutation, unaffected LRRK2, GBA or SNCA mutation carriers, or in sub-sets of PD patients defined by baseline assessments, progression milestones and/or rate of clinical, imaging, genetic mutations, or biomic change. Conduct preliminary verification studies on promising biological markers using stored collected samples.
Study Specific Data Contribution
The following variables and associated data are specific to the PPMI study and are available for analysis as part of AMP PD. These variables have not been harmonized across cohorts, but are relevant to Parkinson's Disease research:
| Assessment/Category | Variable | Definition |
|---|---|---|
| Medical History | PD Surgery (DBS) | Surgery for Parkinson disease |
| Summarized Imaging Data | MRI | MRI results |
| Summarized Imaging Data | DaTSCAN | DaTSCAN SPECT Visual Interpretation Assessment Report |
| Summarized Imaging Data | DTI | DTI Measure (Brain tissue being measured; Left Rostral; Left Middle; Left Caudal; Right Rostral; Right Middle; Right Caudal; Left Reference; Right Reference) |
Tables that Reference these Variables:
- Medical History
- MRI (Magnetic_Resonance_Imaging.csv)
- DaTSCAN_visual_interpretation
- DTI_Regions_of_Interest
Data Type Information:
| Column Name | Data Type | Unique Values |
|---|---|---|
| surgery_for_parkinson_disease | STRING | DBS (Deep Brain Stimulation) |
| mri_results | STRING | Normal; Abnormal, not clinically significant; Abnormal, clinically significant |
| datscan_visual_interpretation | STRING | Negative; Positive |
| DTI | IMAGING |
dti_measure; |
PPMI Inclusion and Exclusion Criteria
Subjects with and without Parkinson’s disease who have a genetic mutation in LRRK2, GBA, or SNCA.
Parkinson's Disease (PD) Subjects - Inclusion
- 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
- A diagnosis of Parkinson disease for 2 years or less at Screening
- Hoehn and Yahr stage I or II at Baseline
- Confirmation from imaging core that screening dopamine transporter SPECT scan is consistent with dopamine transporter deficit (or for sites where DaTSCANTM is not available, that VMAT-2 PET scan is consistent with VMAT deficit)
- Not expected to require PD medication within at least 6 months from Baseline. Male or female age 30 years or older at time of PD diagnosis
Parkinson's Disease (PD) Subjects - Exclusion
- Currently taking levodopa, dopamine agonists, MAO-B inhibitors, 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 60 days
- Received any of the following drugs that might interfere with dopamine transporter SPECT imaging: Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 6 months of Screening
- 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
- Use of investigational drugs or devices within 60 days prior to Baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10)
Healthy Control (HC) Subjects - Inclusion
- Male or female age 30 years or older at Screening
Healthy Control (HC) Subjects - Exclusion
- Current or active clinically significant neurological disorder (in the opinion of the Investigator).
- First degree relative with idiopathic PD (parent, sibling, child)
- MoCA score < 26
- Received any of the following drugs that might interfere with dopamine transporter SPECT imaging: Neuroleptics, metoclopramide, alpha methyldopa,methylphenidate, reserpine, or amphetamine derivative, within 6 months of Screening
- 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
- Use of investigational drugs or devices within 60 days prior to baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10)
SWEDD Subjects - Inclusion
See Section 4.2.1 for Inclusion Criteria for PD subjects. All criteria apply except a SWEDD subject must have confirmation from imaging core that screening dopamine transporter SPECT scan shows no evidence of dopamine transporter deficit (or for sites where DaTSCANTM is not available, that VMAT-2 PET scan shows no evidence of VMAT deficit)
SWEDD Subjects - Exclusion
See Section 4.2.2 for Exclusion Criteria for PD subjects which also apply to SWEDD subjects
Prodromal Subjects - Inclusion
See Section 4.2.7 for Inclusion Criteria. All subjects must demonstrate hyposmia, and/or RBD, plus must be eligible based on DaTSCAN assessment by imaging core
Prodromal Subjects - Exclusion
See Section 4.2.8 for Exclusion Criteria
Genetic Cohort: Parkinson's Disease (PD) subjects - Inclusion
- 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
- A diagnosis of Parkinson disease for 7 years or less at Screening
- Hoehn and Yahr stage < 4 at Baseline
- Male or female age 18 years or older
- Willingness to undergo genetic testing and to be informed of genetic testing results Confirmation of mutation in LRRK2, GBA or SNCA
- For subjects taking any drugs that might interfere with dopamine transporter SPECT imaging (Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative) must be willing and able from a medical standpoint to hold the medication for at least 5 half-lives prior to screening DatSCANTM imaging
Genetic Cohort: Parkinson's Disease (PD) subjects - Exclusion
- 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
Genetic Cohort - Unaffected Individuals Inclusion
- Male or female age 45 years or older at baseline with a LRRK2 or GBA mutation and/or a first degree relative with a LRRK2 or GBA mutation OR Male or female age 30 years or older at baseline with a SNCA mutation and/or a first degree relative with a SNCA mutation
- Unaffected subjects at high risk of LRRK2, GBA or SNCA mutation due to first degree relative with a LRRK2, GBA or SNCA mutation may choose either to be informed of the results or remain unaware of the results
- Unaffected subjects from an ethnic or geographic group known to have relatively high risk of LRRK2, GBA or SNCA mutation (such as people of Ashkenazi Jewish or Basques descent) and who have a family member (either alive or deceased) who has/had PD must be willing to be informed of their own testing results
- Willingness to undergo genetic testing
- For subjects taking any of the following drugs that might interfere with dopamine transporter SPECT imaging (Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative) must be willing and able from a medical standpoint to hold the medication for at least 5 half-lives prior to DatSCAN imaging
Genetic Cohort - Exclusion
- A clinical diagnosis of PD
- 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
Genetic Registry - Inclusion
- Individual with a LRRK2, GBA or SNCA mutation and/or a first degree relative with a LRRK2, GBA or SNCA mutation
- Male or female age 18 years or older
- Willingness to undergo genetic testing, but may choose either to be informed of the results or remain unaware of the results
For further information regarding PPMI inclusion/exclusion criteria, please contact: resources@michaeljfox.org