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

NCT01141023 | Completed Phase 2 DMC

• 1 other identifier: PPMI-001
• Study Type: interventional
• Target: 952
• Locations: 10 countries
• Sites: 33

Brief Summary

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.

Conditions

Parkinson Disease

Keywords

Parkinson; Bio-markers; Neurodegenerative disorder; Imaging; Prodromal

Outcome Measures

Primary Outcomes (1)

• Mean Rates of Change

  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 Outcomes (5)

• Comparison between Rates of Change

  Study intervals ranging from 3 months to 156 months

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

  study intervals ranging from baseline to 156 months.

• Predictive Value

  Baseline to 156 months

• To examine the proportion of SWEDD subjects that have a change in their clinical management at 24 months

  Baseline to 156 Months

• Exploratory Analysis

  Baseline to 156 months

Study Arms (1)

Datscan SPECT Imaging

EXPERIMENTAL

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.

Drug: DaTscan

Interventions

DaTscan DRUG

Also known as: Ioflupane

Datscan SPECT Imaging

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Ken Marek, MD: lead
• Institute for Neurodegenerative Disorders: collaborator

Study Sites (34)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Banner Research Institute

Sun City, Arizona, 85351, United States

Location

University of California San Diego

La Jolla, California, 92093-0948, United States

Location

University of California, San Francisco

San Francisco, California, 94115, United States

Location

The Parkinson's Institute

Sunnyvale, California, 94085, United States

Location

Institute For Neurodegenerative Disorders

New Haven, Connecticut, 06510, United States

Location

Parkinson's Disease& Movement Disorder Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

John Hopkins University

Baltimore, Maryland, 21287, United States

Location

Boston University

Boston, Massachusetts, 02118, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14620, United States

Location

University of Cincinnati/Cincinnati Children's Hospital

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health &Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Univ of Washington and VA Puget Sound Health Care System

Seattle, Washington, 98104, United States

Location

Macquarie University

Sydney, NSW2109, Australia

Location

Innsbruck Medical University

Innsbruck, 6020, Austria

Location

Hospital Pitie-Salpetriere

Paris, 75013, France

Location

Paracelsus-Elena Klinik

Kassel, 34128, Germany

Location

University of Tuebingen

Tübingen, 72076, Germany

Location

Foundation for Biomedical Research of the Academy of Athens

Athens, 11523, Greece

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Universita Federico II

Napoli, 80131, Italy

Location

University of Salerno

Salerno, 84131, Italy

Location

St. Olavs Hospital

Trondheim, 7006, Norway

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Donostia

Donostia / San Sebastian, 20014, Spain

Location

Imperial College London

London, W12 0NN, United Kingdom

Location

Related Publications (17)

• Tsukita K, Kikuya A, Yoshimura K, Nakanishi E, Matsumoto R, Takahashi R. Temporal Dynamics and Cross-Sectional and Longitudinal Factors Associated With Motor Reserve and Outcome in Patients With Parkinson Disease. Neurology. 2026 Jan 27;106(2):e214475. doi: 10.1212/WNL.0000000000214475. Epub 2025 Dec 26.

  PMID: 41453126 DERIVED

• Liu Y, Chen M, Chen P, Lin X, Chen S, Liu C, Wang D, Deng H, Li Q, Wu Y. Machine learning-based stratification of mild cognitive impairment in Parkinson's disease: a multicenter cross-sectional analysis. BMC Med Inform Decis Mak. 2025 Oct 15;25(1):384. doi: 10.1186/s12911-025-03215-0.

  PMID: 41094519 DERIVED

• Tuena C, Repetto C, Ibanez A, Magni G, Stramba-Badiale M, Riva G. Embodied concepts in Parkinson's disease: Insights from fruits versus animals semantic fluency impairments. Neuropsychology. 2025 Oct;39(7):610-618. doi: 10.1037/neu0001026. Epub 2025 Jul 24.

  PMID: 40705614 DERIVED

• Pisani S, Gosse L, Aarsland D, Ray Chaudhuri K, Ballard C, Ffytche D, Velayudhan L, Bhattacharyya S. Parkinson's disease psychosis associated with accelerated multidomain cognitive decline. BMJ Ment Health. 2024 Jul 23;27(1):1-10. doi: 10.1136/bmjment-2024-301062.

  PMID: 39043465 DERIVED

• Park M, Lee YG. Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease. Neurol Genet. 2023 Dec 8;10(1):e200115. doi: 10.1212/NXG.0000000000200115. eCollection 2024 Feb.

  PMID: 38169864 DERIVED

• Tsukita K, Sakamaki-Tsukita H, Kaiser S, Zhang L, Messa M, Serrano-Fernandez P, Takahashi R. High-Throughput CSF Proteomics and Machine Learning to Identify Proteomic Signatures for Parkinson Disease Development and Progression. Neurology. 2023 Oct 3;101(14):e1434-e1447. doi: 10.1212/WNL.0000000000207725. Epub 2023 Aug 16.

  PMID: 37586882 DERIVED

• Wang C, Zhou C, Guo T, Jiaerken Y, Yang S, Xu X, Hu L, Huang P, Xu X, Zhang M. Current coffee consumption is associated with decreased striatal dopamine transporter availability in Parkinson's disease patients and healthy controls. BMC Med. 2023 Jul 25;21(1):272. doi: 10.1186/s12916-023-02994-5.

  PMID: 37491235 DERIVED

• Kim R, Kang N, Byun K, Park K, Jun JS. Prognostic significance of peripheral neutrophils and lymphocytes in early untreated Parkinson's disease: an 8-year follow-up study. J Neurol Neurosurg Psychiatry. 2023 Dec;94(12):1040-1046. doi: 10.1136/jnnp-2022-330394. Epub 2023 Jul 14.

  PMID: 37451695 DERIVED

• Weintraub D, Picillo M, Cho HR, Caspell-Garcia C, Blauwendraat C, Brown EG, Chahine LM, Coffey CS, Dobkin RD, Foroud T, Galasko D, Kieburtz K, Marek K, Merchant K, Mollenhauer B, Poston KL, Simuni T, Siderowf A, Singleton A, Seibyl J, Tanner CM; Parkinson's Progression Markers Initiative. Impact of the Dopamine System on Long-Term Cognitive Impairment in Parkinson Disease: An Exploratory Study. Mov Disord Clin Pract. 2023 Apr 25;10(6):943-955. doi: 10.1002/mdc3.13751. eCollection 2023 Jun.

  PMID: 37332638 DERIVED

• Brumm MC, Pierz KA, Lafontant DE, Caspell-Garcia C, Coffey CS, Siderowf A, Marek K. Updated Percentiles for the University of Pennsylvania Smell Identification Test in Adults 50 Years of Age and Older. Neurology. 2023 Apr 18;100(16):e1691-e1701. doi: 10.1212/WNL.0000000000207077. Epub 2023 Feb 27.

  PMID: 36849448 DERIVED

• Kim R, Park S, Yoo D, Jun JS, Jeon B. Association of Physical Activity and APOE Genotype With Longitudinal Cognitive Change in Early Parkinson Disease. Neurology. 2021 May 11;96(19):e2429-e2437. doi: 10.1212/WNL.0000000000011852. Epub 2021 Mar 31.

  PMID: 33790041 DERIVED

• Simuni T, Brumm MC, Uribe L, Caspell-Garcia C, Coffey CS, Siderowf A, Alcalay RN, Trojanowski JQ, Shaw LM, Seibyl J, Singleton A, Toga AW, Galasko D, Foroud T, Nudelman K, Tosun-Turgut D, Poston K, Weintraub D, Mollenhauer B, Tanner CM, Kieburtz K, Chahine LM, Reimer A, Hutten S, Bressman S, Marek K; Parkinson's Progression Markers Initiative Investigators. Clinical and Dopamine Transporter Imaging Characteristics of Leucine Rich Repeat Kinase 2 (LRRK2) and Glucosylceramidase Beta (GBA) Parkinson's Disease Participants in the Parkinson's Progression Markers Initiative: A Cross-Sectional Study. Mov Disord. 2020 May;35(5):833-844. doi: 10.1002/mds.27989. Epub 2020 Feb 19.

  PMID: 32073681 DERIVED

• Simuni T, Uribe L, Cho HR, Caspell-Garcia C, Coffey CS, Siderowf A, Trojanowski JQ, Shaw LM, Seibyl J, Singleton A, Toga AW, Galasko D, Foroud T, Tosun D, Poston K, Weintraub D, Mollenhauer B, Tanner CM, Kieburtz K, Chahine LM, Reimer A, Hutten SJ, Bressman S, Marek K; PPMI Investigators. Clinical and dopamine transporter imaging characteristics of non-manifest LRRK2 and GBA mutation carriers in the Parkinson's Progression Markers Initiative (PPMI): a cross-sectional study. Lancet Neurol. 2020 Jan;19(1):71-80. doi: 10.1016/S1474-4422(19)30319-9. Epub 2019 Oct 31.

  PMID: 31678032 DERIVED

• Simuni T, Caspell-Garcia C, Coffey CS, Weintraub D, Mollenhauer B, Lasch S, Tanner CM, Jennings D, Kieburtz K, Chahine LM, Marek K. Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson's disease: the PPMI cohort. J Neurol Neurosurg Psychiatry. 2018 Jan;89(1):78-88. doi: 10.1136/jnnp-2017-316213. Epub 2017 Oct 6.

  PMID: 28986467 DERIVED

• Latourelle JC, Beste MT, Hadzi TC, Miller RE, Oppenheim JN, Valko MP, Wuest DM, Church BW, Khalil IG, Hayete B, Venuto CS. Large-scale identification of clinical and genetic predictors of motor progression in patients with newly diagnosed Parkinson's disease: a longitudinal cohort study and validation. Lancet Neurol. 2017 Nov;16(11):908-916. doi: 10.1016/S1474-4422(17)30328-9. Epub 2017 Sep 25.

  PMID: 28958801 DERIVED

• Smith KM, Xie SX, Weintraub D. Incident impulse control disorder symptoms and dopamine transporter imaging in Parkinson disease. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):864-70. doi: 10.1136/jnnp-2015-311827. Epub 2015 Nov 3.

  PMID: 26534930 DERIVED

• Oliveira FP, Castelo-Branco M. Computer-aided diagnosis of Parkinson's disease based on [(123)I]FP-CIT SPECT binding potential images, using the voxels-as-features approach and support vector machines. J Neural Eng. 2015 Apr;12(2):026008. doi: 10.1088/1741-2560/12/2/026008. Epub 2015 Feb 24.

  PMID: 25710187 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Neurodegenerative Diseases

Interventions

ioflupane

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies

Study Officials

• Kenneth L Marek, MD

  Institute for Neurodegenerative Disorders

  STUDY CHAIR

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Study Chair

Study Record Dates

• First Submitted: June 8, 2010
• First Posted: June 10, 2010
• Study Start: June 1, 2010
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: November 14, 2023

Record last verified: 2023-11

Locations

AU (1); GR (1); NO (1); IT (2); GB (1); ES (2); US (21); DE (2); FR (1); IL (1)