Study to Identify Clinical, Imaging and Biologic Markers of Parkinson Disease Progression (PPMI)

November 13, 2023 updated by: Ken Marek, MD

The Parkinson's Progression Markers Initiative (PPMI)

This is a observational, multi-center study to assess progression of clinical features, imaging and biologic biomarkers in Parkinson disease (PD) patients compared to healthy controls (HC) and in PD patient subtypes.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Amendment 14 - 26-Mar-2018 Revised to reflect the implementation of PPMI Wearables and Sensor Study Companion Protocol

Amendment 13 - 20-Nov-2017 Extension of study duration until 2023 for all cohorts (except Genetic Registry).

Amendment 12 - 01-Jun-2017 Planned date of trial extended to September 30, 2020 Ceasing new enrollments into the Genetic Registry for LRRK2 and GBA subjects Added Sensor - PPMI Companion Study Allow for consent to share contact information with FOUND team at any visit. Incorporation of Parkinson's Disease Risk Factor Questionnaire (PD-RFQ) into FOUND.

Amendment 11 - 01-Apr-2016 Added the collection of peripheral blood mononuclear cells (PBMC) from blood samples at interim visits.

Addition of PPMI Pathology Core/PPMI Brain and Tissue Bank Addition of Gait Assessment Companion Study (Select PPMI sites - Genetic Cohort only) Testing for additional GBA mutations - previously testing involved testing only for the GBA N370S mutation; however, going forward, testing will include tests for additional GBA mutations that are identified as being associated with certain ancestry.

Amendment 10 - 05-Oct-2015 Extended study period for PD and Healthy Control subjects through 8 years. For Prodromal subjects (RBD and Hyposmic) added iPSC companion study.

Amendment 9 - 01-Nov-2014 Addition of GBA throughout to document additional testing for GBA mutation. Allocation of subjects in Genetic Cohort and Genetic Registry revised to account for inclusion of GBA subjects.

Amendment 8 - 12-May-2014 Companion Protocols: skin biopsy/stem cell; Amyloid Imaging 18F Florbetaben; Family History Sub-Study; FOUND in PPMI registry. More detailed description of new procedures including: Advance directive for clinical research participation; Extension of study period (for SWEDDs with positive scans at Yr. 2) by continuing or re-inviting to study and followed (as per PD subjects through Month 60); Objective Parkinson Disease Measurement (OPDM) finger tapping measurement.

Amendment 7 - 14-Oct-2013 Pre-Screening Prodromal - RBD clarifications Pre-Screening Genetic Cohort - clarified Assessments/tests clarified, including addition of consent (or withdrawal of consent, if applicable) for future contact about future studies and PD family history data collection for Genetic cohort subjects as selected visits.

Amendment 6 - 29-May-2013 Genetics Coordination Core is added to study. The GCC included Genetic Cohort PD Subjects, Genetic Cohort Unaffected Subjects and Genetic Registry Subjects.

Amendment 5 - 27-Nov-2012 Olfactory and RBD subjects added as the Prodromal cohort.

Amendment 4 - 30-Mar-2012 Addition of 18F-AV-133 VMAT-2 PET Imaging for participating U.S. sites and Australia. (Refer to 18F-AV-133-PPMI companion protocol).

Number of sites increased from 21 to 24. Addition of cognitive categorization and diagnostic features assessments.

Amendment 3 - 15-Jul-2011 Addition of SWEDD subjects to study design. Blood Sampling Advisement to collect research samples in a fasted state.

Amendment 2 - 19-May-2011 Changed visit window from 30 days to 45 days for Baseline visit to be completed.

Section on DAT and SPECT Imaging - section changed to account for subject travel to the Institute for Neurodegenerative Disorders to conduct SPECT scanning and injection of either DaTSCAN or BCIT.

Main Protocol - PPMI will be a five-year natural history study (a minimum of 3-year involvement for each subject) of de novo idiopathic PD patients and healthy controls. This study will also include a SWEDD (subjects without evidence of dopaminergic deficit)and Prodromal populations.

All subjects will be comprehensively assessed at baseline and every three to six months thereafter. Subjects will undergo clinical (motor, neuropsychiatric and cognitive) and imaging assessments and will donate blood, urine, and cerebral spinal fluid (CSF). A blood sample for DNA will be collected. Data will be collected by each site under uniformly established protocols and data will be analyzed and stored at designated core facilities.

Study Type

Interventional

Enrollment (Actual)

952

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Sydney, Australia, NSW2109
        • Macquarie University
      • Innsbruck, Austria, 6020
        • Innsbruck Medical University
      • Paris, France, 75013
        • Hospital Pitie-Salpetriere
      • Kassel, Germany, 34128
        • Paracelsus-Elena Klinik
      • Tuebingen, Germany, 72076
        • University of Tuebingen
      • Athens, Greece, 11523
        • Foundation for Biomedical Research of the Academy of Athens
      • Tel Aviv, Israel, 64239
        • Tel Aviv Sourasky Medical Center
      • Napoli, Italy, 80131
        • Università Federico II
      • Salerno, Italy, 84131
        • University of Salerno
      • Trondheim, Norway, 7006
        • St. Olavs Hospital
      • Barcelona, Spain, 08036
        • Hospital Clinic De Barcelona
      • San Sebastian, Spain, 20014
        • Hospital Donostia
      • London, United Kingdom, W12 0NN
        • Imperial College London
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • Arizona
      • Sun City, Arizona, United States, 85351
        • Banner Research Institute
    • California
      • La Jolla, California, United States, 92093-0948
        • University of California San Diego
      • San Francisco, California, United States, 94115
        • University of California, San Francisco
      • Sunnyvale, California, United States, 94085
        • The Parkinson's Institute
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Institute for Neurodegenerative Disorders
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Parkinson's Disease& Movement Disorder Center of Boca Raton
      • Tampa, Florida, United States, 33606
        • University of South Florida
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Emory University School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • John Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston University
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10003
        • Beth Israel Medical Center
      • Rochester, New York, United States, 14620
        • University of Rochester
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati/Cincinnati Children's Hospital
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health &Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • University of Pennsylvania
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
    • Washington
      • Seattle, Washington, United States, 98104
        • Univ of Washington and VA Puget Sound Health Care System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

28 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Parkinson Disease (PD) Subjects:

  • A diagnosis of Parkinson disease for 2 years or less at Screening.
  • Confirmation from imaging core that screening DAT scan is consistent with dopamine transporter deficit, or if applicable a VMAT-2 PET scan consistent with vesicular monoamine transporter deficit.
  • Not expected to require PD medication with at least 6 months from Baseline.
  • Male or female age 30 years or older at time of PD diagnosis.

Healthy Control (HC) Subjects:

• Male or female age 30 years or older at Screening.

Exclusion Criteria:

Parkinson Disease (PD) Subjects:

  • 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 DAT 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.

If applicable, currently taking medications that are known to cause QT-prolongation, or are currently taking tetrabenazine (TBZ or amphetamine type medications.

  • 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 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:

  • Current or active neurological disorder.
  • First degree relative with idiopathic PD (parent, sibling, child).
  • MoCA score < 26.
  • Received any of the following drugs that might interfere with DAT imaging: Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 6 months of Screening.

If applicable, currently taking medications that are known to cause QT-prolongation, or are currently taking tetrabenazine (TBZ) or amphetamine type medications.

  • 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 other investigational drugs within 60 days prior to baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10).

SWEDD Subjects:

All PD criteria apply, as above, except a SWEDD subject must have confirmation from imaging core that screening dopamine transporter SPECT scan shows no evidence of dopamine transporter deficit or if applicable a VMAT-2 PET scan shows no evidence of vesicular monoamine transporter deficit.

Prodromal Subjects:

Inclusion Criteria (Prodromal Subjects) 4.2.7.1. Subjects must have at least one of the following characteristics:

Hyposmia:

  1. Male or female age 60 years or older
  2. Confirmation from olfactory core that olfaction as determined by UPSIT is at or below the 10th percentile by age and gender

REM Behavior Disorder (RBD):

  1. Male or female age 60 years or older
  2. Confirmation from sleep core that subject's Polysomnography (PSG) meets criteria for RBD

LRRK2:

  1. Male or female age 60 years or older
  2. Written confirmation or documentation from testing facility that the individual is LRRK2 mutation positive 4.2.7.2. Confirmation from imaging core that screening dopamine transporter SPECT scan is read as eligible (see below). About 80 subjects will have a range of DAT deficit similar to subjects with early PD (mild to moderate DAT deficit). About 20 subjects will be selected with no DAT deficit or minimal DAT deficit similar in age, gender, and risk profile to those with mild to moderate DAT deficit. 4.2.7.3. Ability to provide written informed consent in accordance with Good Clinical Practice (GCP), International Conference on Harmonization (ICH), and local regulations. 4.2.7.4. Willing and able to comply with scheduled visits, required study procedures and laboratory tests. 4.2.7.5. Women may not be pregnant, lactating or planning pregnancy during the course of the study. Includes a negative urine pregnancy test on day of screening scan prior to injection (DaTSCAN).

Exclusion Criteria (Prodromal Subjects)

  1. Current or active clinically significant neurological disorder or psychiatric disorder (in the opinion of the Investigator).
  2. GDS score greater than or equal to 10 (GDS score of 5 - 9 requires Investigator discretion to enter study).
  3. STAI Form Y-1 greater than or equal to 54 requires Investigator discretion to enter study.
  4. A clinical diagnosis of dementia63 as determined by the investigator (Appendix 1).
  5. A clinical diagnosis of Parkinson disease at the Screening visit as determined by the Investigator.
  6. 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.
  7. Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude safe completion of the lumbar puncture.
  8. Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
  9. Any other medical or psychiatric condition or lab abnormality, which in the opinion of the investigator might preclude participation.
  10. 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).
  11. Previously obtained MRI scan with evidence of clinically significant neurological disorder (in the opinion of the Investigator).

Genetic Cohort: Parkinson Disease Subjects - Inclusion:

  1. Patients must have at least two of the following: resting tremor, bradykinesia, rigidity (must have either resting remor or bradykinesia) or either asymmetric resting tremor or asymmetric bradykinesia.
  2. A diagnosis of Parkinson Disease for 7 years or less at screening.
  3. Hoehn and Yahr state <4 at baseline
  4. Male or female age 18 years or older
  5. Willingness to undergo genetic testing and to be informed of genetic testing results.
  6. Confirmation of mutation in LRRK2, GBA or SNCA
  7. 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 DatSCAN(TM) imaging.

Exclusion:

  1. Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude safe completion of the lumbar puncture.
  2. 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:

  1. Male or female age 45 years or older at baseline with LRRK2 or GBA mutation and/or first degree relative with a LRRK2 or GBA mutation or
  2. Male or female age 30 years or older at baseline with a SNCA mutation and/or a first degree relative with a SNCA mutation.
  3. 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.
  4. Unaffected subjects from an ethnic or geographic group knkown 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.
  5. Willingness to undergo genetic testing
  6. 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.

Exclusion:

  1. A clinical diagnosis of PD
  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.

Genetic Registry - Inclusion:

  1. Individual with a LRRK2, GBA or SNCA mutation and/or a first degree relative with a LRRK2, GBA or SNCA mutation.
  2. Male or female age 18 years or older
  3. Willingness to undergo genetic testing, but may choose either to be informed of the results or remain unaware of the results.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Datscan SPECT Imaging
Subjects will b injected with 3-5 mCi of dopamine transporter. Within a 4 hour (+/- 30 minutes) window following the injection, subjects will undergo SPECT imaging on the camera.
Other Names:
  • Ioflupane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Rates of Change
Time Frame: Baseline to 156 months
The mean rates of change and the variability around the mean of clinical, imaging and biomic outcomes in early PD patients, and where appropriate the comparison of these rates between PD patient subsets and between various subsets (including, but not limited to: PD vs. healthy subjects, PD vs. SWEDD, PD vs. prodromal, PD with and without LRRK2, GBA or SNCA mutation, unaffected LRRK2, GBA or SNCA mutation carriers vs. healthy controls) at study intervals ranging from 3 months to 36 months. Specific examples of outcomes include MDS-UPDRS, dopamine transporter imaging striatal uptake, vesicular monoamine transporter type-2 uptake, and serum and CSF alpha-synuclein. PD patient subsets may be defined by baseline assessments, genetic mutations, progression milestones and/or rate of clinical, imaging, or biomic change.
Baseline to 156 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison between Rates of Change
Time Frame: Study intervals ranging from 3 months to 156 months
Comparison between the rates of change in the mean of clinical, imaging and biomic outcomes in various subsets (including, but not limited to: early PD vs. healthy subjects, PD vs. SWEDD, PD vs. prodromal, PD with and without LRRK2, GBA or SNCA mutation, unaffected LRRK2, GBA or SNCA mutation vs. healthy controls)
Study intervals ranging from 3 months to 156 months
Prevalence of measures of clinical, imaging and biomic outcomes in various subsets (
Time Frame: study intervals ranging from baseline to 156 months.
Including, but not limited to: early PD patients, healthy subjects, PD vs SWEDDs, PD vs prodromal, PD with and without LRRK2, GBA or SNCA mutation, unaffected LRRK2, GBA or SNCA mutation carriers vs. healthy subjects.
study intervals ranging from baseline to 156 months.
Predictive Value
Time Frame: Baseline to 156 months
To establish the predictive value of early clinical non-motor features, baseline imaging and biomic outcomes for future course of disease.
Baseline to 156 months
To examine the proportion of SWEDD subjects that have a change in their clinical management at 24 months
Time Frame: Baseline to 156 Months
SWEDD Clinical Diagnosis and Management Questionnaire.
Baseline to 156 Months
Exploratory Analysis
Time Frame: Baseline to 156 months
Exploratory analysis to estimate the percentage of Prodromal subjects with one or more risk characteristics [hyposmia (<10th percentile for age and gender), RBD, or LRRK2, GBA or SNCA genetic mutation, and baseline DaTSCAN binding showing minimal to moderate DAT deficit] that phenoconvert to PD within 2 years, and an exploratory analysis to examine whether the baseline DaTSCAN binding or progression of clinical, imaging, or biospecimen markers may predict those subjects likely to phenoconvert.
Baseline to 156 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Chair: Kenneth L Marek, MD, Institute for Neurodegenerative Disorders
  • Study Director: John Q. Trojanowski, MD, PhD, University of Pennsylvania
  • Study Director: Arthur W. Toga, PhD, University of California, Los Angeles
  • Study Director: Tatiana Froud, PhD, Indiana University
  • Study Director: Karl Kieburtz, MD, Clinical Trials Coordination Center
  • Study Director: Andrew Singleton, PhD, Laboratory of Neurogenetics; National Institute on Aging NIH
  • Study Director: John P Seibyl, MD, Institute for Neurodegenerative Disorders
  • Study Director: Christopher Coffey, PhD, Clinical Trials Statistical and Data Management Center, University of Iowa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2010

Primary Completion (Actual)

June 30, 2020

Study Completion (Actual)

June 30, 2020

Study Registration Dates

First Submitted

June 8, 2010

First Submitted That Met QC Criteria

June 8, 2010

First Posted (Estimated)

June 10, 2010

Study Record Updates

Last Update Posted (Actual)

November 14, 2023

Last Update Submitted That Met QC Criteria

November 13, 2023

Last Verified

November 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Parkinson Disease

Clinical Trials on DaTscan

Subscribe