PPMI Clinical - Establishing a Deeply Phenotyped PD Cohort

NCT04477785 | Recruiting

• 1 other identifier: PPMI-002
• Study Type: observational
• Target: 4,500
• Locations: 12 countries
• Sites: 50

Brief Summary

The Parkinson Progression Marker Initiative (PPMI) 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 is to identify markers of disease progression for use in clinical trials of therapies to reduce progression of PD disability.

Conditions

Parkinson Disease

Keywords

Parkinson; Bio-markers; Neurodegenerative disorder; Imaging; Prodromal; Genetics; At Risk; Loss of Smell

Outcome Measures

Primary Outcomes (5)

• Establish standardized protocols for acquisition, transfer and analysis of clinical, digital, imaging, biologic and genetic data that can be used by the PD research community.

  This protocol will build on the existing PPMI infrastructure

  Baseline to 156 months

• Comprehensive and uniformly acquired dataset

  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)

  Baseline to 156 months

• Comparison between Rates of Change

  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 variants (such as Parkin or Pink1) and individuals with prodromal Parkinson's disease (including individuals with REM sleep behavior disorder (RBD)), olfactory loss, LRRK2, GBA, SNCA or rare genetic variants (such as Parkin or Pink1) and/or other risk factors for PD with and without dopamine transporter (DAT) deficit and in healthy participants.

  Study intervals ranging from 3 months to 156 months

• Prevalence of measures of clinical, imaging and biomic outcomes in various subsets

  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 variants (such as Parkin or Pink1)) and individuals with prodromal Parkinson's disease (including individuals with RBD, olfactory loss, a LRRK2, GBA, SNCA or rare genetic variants (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.

  study intervals ranging from baseline to 156 months.

• Establish the probability of phenoconversion to PD

  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 variants (such as Parkin or Pink1) and/ or other risk factors for PD with and without DAT deficit).

  study intervals ranging from baseline to 156 months.

Study Arms (1)

Clinical Observation

In PPMI Clinical up to 4,500 participants will be enrolled and followed longitudinally once identified, over the course of 5-8 years.

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

In PPMI Clinical up to 4,500 participants will be enrolled and followed longitudinally from approximately 50-55 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).

You may qualify if:

• Male or female age 57 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 SPECT imaging.
• Confirmation that participant is eligible based on Screening SPECT imaging.
• Able to provide informed consent.
• 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.

You may not qualify if:

• First degree relative with PD (i.e., biologic parent, sibling, child).
• Current or active clinically significant neurological disorder (in the opinion of 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 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.
• Any other reason that, in the opinion of the investigator, would render the participant unsuitable for study enrollment.
• 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).
• Male or female age 30 years or older at Screening Visit.
• A diagnosis of Parkinson's disease for 2 years or less at Screening Visit.
• Not expected to require PD medication within 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 SPECT imaging.

Sponsors & Collaborators

• Institute for Neurodegenerative Disorders: collaborator
• Michael J. Fox Foundation for Parkinson's Research: lead

Study Sites (50)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

RECRUITING

Mayo Foundation for Medical Education and Research

Scottsdale, Arizona, 85259, United States

RECRUITING

Banner Research Institute

Sun City, Arizona, 85351, United States

RECRUITING

University of California San Diego

La Jolla, California, 92093-0948, United States

RECRUITING

Keck School of Medicine of USC

Los Angeles, California, 90033, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94115, United States

RECRUITING

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Institute For Neurodegenerative Disorders

New Haven, Connecticut, 06510, United States

RECRUITING

Parkinson's Disease& Movement Disorder Center of Boca Raton

Boca Raton, Florida, 33486, United States

RECRUITING

University of Florida

Gainesville, Florida, 32608, United States

RECRUITING

University of South Florida

Tampa, Florida, 33606, United States

RECRUITING

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

Boston University

Boston, Massachusetts, 02118, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02446, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 89106, United States

RECRUITING

Beth Israel Medical Center

New York, New York, 10003, United States

RECRUITING

NYU Langone Health

New York, New York, 10017, United States

RECRUITING

University of Rochester

Rochester, New York, 14620, United States

RECRUITING

University of Cincinnati/Cincinnati Children's Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Oregon Health &Science University

Portland, Oregon, 97239, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Univ of Washington and VA Puget Sound Health Care System

Seattle, Washington, 98104, United States

RECRUITING

Innsbruck Medical University

Innsbruck, 6020, Austria

RECRUITING

The Ottawa Hospital - Civic Campus

Ottawa, Ontario, K1Y 4E9, Canada

RECRUITING

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

RECRUITING

McGill University

Montreal, Quebec, H3A2B4, Canada

RECRUITING

Philipps-University of Marburg

Hessen, 35043, Germany

RECRUITING

Paracelsus-Elena Klinik

Kassel, 34128, Germany

RECRUITING

University of Luebeck

Lübeck, 23562, Germany

RECRUITING

University of Tuebingen

Tübingen, 72076, Germany

RECRUITING

Foundation for Biomedical Research of the Academy of Athens

Athens, Athens, 11523, Greece

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, Tel Aviv, 64239, Israel

RECRUITING

University of Salerno

Salerno, Salerno, 84131, Italy

RECRUITING

Parkinson Research Clinic

Luxembourg, L-1257, Luxembourg

RECRUITING

Radboud University

Nijmegen, Gelderland, 6525 GC, Netherlands

RECRUITING

Lagos College of Medicine, University of Lagos

Lagos, Lagos, 121010, Nigeria

RECRUITING

Hospital Clinic de Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

Hospital Donostia

Donostia / San Sebastian, San Sebastian, 20014, Spain

RECRUITING

Queen Mary University of London

London, Britain, EC1M 6BQ, United Kingdom

RECRUITING

Newcastle University

Newcastle upon Tyne, Tyne and Wear, NE45PL, United Kingdom

RECRUITING

Imperial College London

London, W12 0NN, United Kingdom

RECRUITING

John Radcliffe Hospital Oxford and Oxford University

Oxford, Oxford, OX3 9DU, United Kingdom

RECRUITING

Related Publications (1)

• Pacheco Pachado M, Casas AI, Elbatreek MH, Nogales C, Guney E, Espay AJ, Schmidt HHHW. Re-Addressing Dementia by Network Medicine and Mechanism-Based Molecular Endotypes. J Alzheimers Dis. 2023;96(1):47-56. doi: 10.3233/JAD-230694.

  PMID: 37742653 DERIVED

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.

MeSH Terms

Conditions

Parkinson Disease; Neurodegenerative Diseases; Anosmia

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Olfaction Disorders; Sensation Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Kenneth L Marek, MD

  Institute for Neurodegenerative Disorders

  PRINCIPAL INVESTIGATOR

• Caroline Tanner, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cari Rainville, BS

CONTACT

877-525-7764; crainville@indd.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Protocol Co- Principal Investigator

Study Record Dates

• First Submitted: July 15, 2020
• First Posted: July 20, 2020
• Study Start: July 1, 2020
• Primary Completion (Estimated): December 1, 2033
• Study Completion (Estimated): December 1, 2033
• Last Updated: June 12, 2026

Record last verified: 2025-10

Locations

NG (1); IL (1); US (30); GR (1); ES (2); NL (1); GB (4); AU (1); IT (1); DE (4); CA (3); LU (1)