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Long-term observation of Parkinson's disease progression and biomarkers

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

Observational Michael J. Fox Foundation for Parkinson's Research · NCT04477785

This study is trying to track how Parkinson's disease changes over time in people with the condition, those at risk, and healthy individuals to find signs that can help in future treatments.

Quick facts

Study typeObservational
Enrollment4500 (estimated)
Ages30 Years and up
SexAll
SponsorMichael J. Fox Foundation for Parkinson's Research Academic / other
Locations50 sites (Birmingham, Alabama and 49 other locations)
Trial IDNCT04477785 on ClinicalTrials.gov

What this trial studies

The Parkinson Progression Marker Initiative (PPMI) is a longitudinal, observational study designed to track the progression of Parkinson's disease (PD) through clinical features, digital outcomes, and various biomarkers. Participants include individuals with manifest PD, those in the prodromal stage, and healthy controls. The study aims to identify reliable markers of disease progression that can be utilized in future clinical trials aimed at reducing PD-related disability. Participants may also be involved in additional PPMI initiatives as they develop.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 57 and older, both with Parkinson's disease and healthy controls.

Not a fit: Patients who are younger than 57 or those with advanced Parkinson's disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to the identification of biomarkers that help in monitoring and potentially slowing the progression of Parkinson's disease.

How similar studies have performed: Other studies focusing on biomarkers and progression in neurodegenerative diseases have shown promise, indicating that this approach has potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Birmingham, Alabama and 49 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Parkinson DiseaseParkinsonBio-markersNeurodegenerative disorderImagingProdromalGeneticsAt Risk
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.