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

Brief Summary

Official Title: “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 Type: Interventional
  • Study Design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
  • Study Primary Completion Date: September 2017

Detailed Clinical Trial 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.

Interventions Used in this Clinical Trial

  • Drug: Datscan and AV-133

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: Datscan and AV-133

Outcome Measures for this Clinical Trial

Primary 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
      Safety Issue?: No

Secondary 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
      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.
      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.
      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
      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
      Safety Issue?: No
  • To examine the proportion of Prodromal subjects with one or more risk characteristics.
    • Time Frame: No Time Frame needed
      Safety Issue?: No
  • 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
      Safety Issue?: No
  • 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
      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
      Safety Issue?: No
  • 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
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: Accepts Healthy Volunteers

Clinical Trial Investigator Information

  • Lead Sponsor
    • Ken Marek, MD
  • Collaborator
    • Institute for Neurodegenerative Disorders
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Ken Marek, MD, Study Chair – Michael J. Fox Foundation for Parkinson’s Research
  • Overall Official(s)
    • Kenneth L Marek, MD, Study Chair, Institute for Neurodegenerative Disorders
    • John Q. Trojanowski, MD, PhD, Principal Investigator, University of Pennsylvania
    • Arthur W. Toga, PhD, Principal Investigator, University of California, Los Angeles
    • Alison Ansbach, MS, Principal Investigator, Coriell Institute for Medical Research
    • Karl Kieburtz, MD, Principal Investigator, Clinical Trials Coordination Center
    • Andrew Singleton, PhD, Principal Investigator, Laboratory of Neurogenetics; National Institute on Aging NIH
    • John P Seibyl, MD, Principal Investigator, Institute for Neurodegenerative Disorders
    • Christopher Coffey, PhD, Principal Investigator, Clinical Trials Statistical and Data Management Center, University of Iowa

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01141023