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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Michael J. Fox Foundation for Parkinson's Research
Sponsor:
Collaborator:
Institute for Neurodegenerative Disorders
Information provided by (Responsible Party):
Ken Marek, MD, Michael J. Fox Foundation for Parkinson's Research
ClinicalTrials.gov Identifier:
NCT01141023
First received: June 8, 2010
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Parkinson Disease
Drug: Datscan and AV-133
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: The Parkinson's Progression Markers Initiative (PPMI)

Resource links provided by NLM:


Further study details as provided by Michael J. Fox Foundation for Parkinson's Research:

Primary Outcome Measures:
  • The mean rates of change and the variability around the mean of clinical, imaging and biomic outcomes in early PD patients, and the comparison of these rates between PD patient subsets and between PD, SWEDD, Prodromal and healthy subjects. [ Time Frame: Study intervals from 3 months - 36 months ] [ Designated as safety issue: No ]
    Specific examples of outcomes include MDS-UPDRS, dopamine transporter striatal uptake, vesicular monoamine transporter type-2 uptake, and serum and CSF alpha-synuclein. PD patient subsets maybe defined by baseline assessments, progression milestones and/or rate of clinical,imaging, or biomic change.


Secondary Outcome Measures:
  • Comparison between the rates of change in the mean of clinical, imaging and biomic outcomes in early PD patients and between PD and healthy subjects [ Time Frame: Study Intervals from 3 months to 36 months ] [ Designated as safety issue: No ]
  • Prevalence of measures of clinical, imaging and biomic outcomes in early PD patients and healthy subjects. [ Time Frame: from baseline to 36 months. ] [ Designated as safety issue: No ]
  • To establish the predictive value of early clinical non-motor features, baseline imaging and biomic outcomes for future course of disease. [ Time Frame: No time frame needed. ] [ Designated as safety issue: No ]
  • Exploratory analysis of comparison between the rates of change in the mean of clinical, imaging and biomic outcomes in prodromal PD with baseline DaTSCAN binding showing minimal to moderate DAT deficit and early PD patients and healthy subjects. [ Time Frame: Study intervals from 3 months to 36 months ] [ Designated as safety issue: No ]
  • Exploratory analysis of prevalence of measures of clinical, imaging and biomic outcomes in prodromal PD compared to early PD patients and healthy subjects [ Time Frame: Study intervals from baseline to 36 months ] [ Designated as safety issue: No ]
  • To examine the proportion of Prodromal subjects with one or more risk characteristics. [ Time Frame: No Time Frame needed ] [ Designated as safety issue: No ]
    To examine the proportion of Prodromal subjects with one or more risk characteristics [hyposmia (<10th percentile by age and gender), RBD, or LRRK2 mutation, and baseline DaTSCAN binding showing minimal to moderate DAT deficit] who phenoconvert within two years. To correlate the baseline DaTSCAN binding with risk of phenoconversion.

  • To conduct exploratory analyses to examine whether the progression of clinical, imaging, and biospecimen biomarkers will predict those subjects likely to phenoconvert. [ Time Frame: No Time frame needed ] [ Designated as safety issue: No ]
    For example, dopamine transfer loss during the prodromal period either independently or in combination with other biomarkers may provide a quantitative outcome associated with prodromal disease progression to phenoconversion.

  • To examine the proportion of SWEDD subjects that have a change in their clinical management at 24 months (SWEDD Clinical Diagnosis and Management Questionnaire). [ Time Frame: No Time Frame Needed ] [ Designated as safety issue: No ]
  • To conduct exploratory analyses in SWEDD subjects to examine the prevalence of measures of clinical, imaging, and biomic outcomes from baseline to 24 months. [ Time Frame: Interval 3 months to 24 months ] [ Designated as safety issue: No ]
    Examine the mean rates of change and the variability among these outcomes from 3 months to 24 months, and to examine the correlations between the rates of change in these outcomes from 3 months to 24 months.

  • To conduct exploratory analyses to determine whether the measures and change over time in clinical, imaging, and biomic outcomes are similar among the SWEDD, Prodromal, and PD subjects. [ Time Frame: No Time Frame Needed ] [ Designated as safety issue: No ]

Estimated Enrollment: 680
Study Start Date: June 2010
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Datscan and AV-133 Drug: Datscan and AV-133

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01141023

  Show 24 Study Locations
Sponsors and Collaborators
Ken Marek, MD
Institute for Neurodegenerative Disorders
Investigators
Study Chair: Kenneth L Marek, MD Institute for Neurodegenerative Disorders
Principal Investigator: John Q. Trojanowski, MD, PhD University of Pennsylvania
Principal Investigator: Arthur W. Toga, PhD University of California, Los Angeles
Principal Investigator: Alison Ansbach, MS Coriell Institute for Medical Research
Principal Investigator: Karl Kieburtz, MD Clinical Trials Coordination Center
Principal Investigator: Andrew Singleton, PhD Laboratory of Neurogenetics; National Institute on Aging NIH
Principal Investigator: John P Seibyl, MD Institute for Neurodegenerative Disorders
Principal Investigator: Christopher Coffey, PhD Clinical Trials Statistical and Data Management Center, University of Iowa
  More Information

No publications provided

Responsible Party: Ken Marek, MD, Study Chair, Michael J. Fox Foundation for Parkinson's Research
ClinicalTrials.gov Identifier: NCT01141023     History of Changes
Other Study ID Numbers: PPMI-001
Study First Received: June 8, 2010
Last Updated: October 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Michael J. Fox Foundation for Parkinson's Research:
Parkinson
Bio-markers
Neurodegenerative disorder
Imaging
Prodromal

Additional relevant MeSH terms:
Parkinson Disease
Disease Progression
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on August 28, 2014