PPMI Update. Ken Marek. PPMI Annual Meeting May 13, 2015 New York, NY

Transcription

1 PPMI Update Ken Marek PPMI Annual Meeting May 13, 2015 New York, NY

2 67 yo right handed WF in excellent general health History 6 month history of poor tennis play Note 1-2 years mild constipation 2 months intermittent R UE tremor while reading the newspaper, or if in stressful situation Exam Mild R UE resting tremor Reduced R arm swing PD DIAGNOSIS 1 MONTH AGO IF THE SYMPTOMS REMAIN AS THEY ARE NOW I COULD DEAL WITH THIS PD patient MAY 2011 MAY 2013 Two years progression History Continue to work, all activities Requires sinemet 100 mg tid Worried about future Exam Mild R UE> L UE resting tremor R brady UE>LE PD DIAGNOSIS 24 MONTHS AGO THESE SYMPTOMS ARE ANNOYING AND I WORRY THAT THEY ARE GETTING WORSE. Four years progression History Continue to work, more difficulty with keyboards etc Requires sinemet 100 mg tid, SSRI not working as reliably Worried about progression, cognition Exam MAY 2015 Mild R UE> L UE resting tremor, R brady UE>LE Gait stiff, subtle balance Minor fluctuations PD DIAGNOSIS 48 MONTHS AGO HOW CAN I STOP TIS FROM GETTING WORSE.

3 PPMI Biomarker Infrastructure Parkinson s Progression Markers Initiative Specific Data Set Appropriate population (early stage PD and controls, prodromal, genetic PD subjects) Clinical (motor/non-motor) and imaging data Corresponding biologic samples (DNA, blood, CSF) Standardization Uniform collection of data and samples Uniform storage of data and samples Strict quality control/quality assurance Access/Sharing Data available to research community data mining, hypothesis generation & testing Samples available for studies

4 Requirements for Biomarker Infrastructure Parkinson s Progression Markers Initiative Specific Data Set Appropriate population (early stage PD and controls) Clinical (motor/non-motor) and imaging data Corresponding biologic samples (DNA, blood, CSF) Standardization Uniform collection of data and samples Uniform storage of data and samples Strict quality control/quality assurance Access/Sharing Data available to research community data mining, hypothesis generation & testing Samples available for studies

5 PPMI Study Details: Synopsis Study population Assessments/ Clinical data collection Biologic collection/ Data and Biosamples shared on website de novo PD subjects (newly diagnosed and unmedicated) 200 age- and gender-matched healthy controls 70 SWEDD Subjects will be followed for 3 to 5 years Motor assessments Neurobehavioral/cognitive testing Autonomic, Olfaction, Sleep DaTSCAN imaging, DTI/RS MRI DNA collected at screening Serum and plasma collected at each visit; urine collected annually CSF collected at baseline, 6mo 12 mo and then annually Samples aliquotted and stored in central biorepository >370,000 Data downloads > 100 Sample requests via BRC Ancillary study development

6 PPMI Study Details: Synopsis Study population Assessments/ Clinical data collection Biologic collection/ Data and Biosamples shared on website de novo PD subjects (newly diagnosed and unmedicated) 200 age- and gender-matched healthy controls 70 SWEDD 70 Prodromal - Olfactory/RBD 250 LRRK2 - PD manifest and non-manifesting family members 250 GBA- PD manifest and non-manifesting family members 100 SNCA - PD manifest and non-manifesting family members Subjects will be followed for 3 to 5 years Motor assessments Neurobehavioral/cognitive testing Autonomic, Olfaction, Sleep DaTSCAN, AV133, DTI/RS MRI, Amyloid DNA collected at screening Serum and plasma collected at each visit; urine collected annually CSF collected at baseline, 6mo 12 mo and then annually Samples aliquotted and stored in central biorepository >370,000 Data downloads > 100 Sample requests via BRC Ancillary study development

7 ENROLLMENT GROUP Consented Enrolled Withdrawn Active Complete PD Subjects Healthy Controls SWEDD Subjects Prodromal Hyposmic Prodromal RBD LRRK2 PD Cohort LRRK2 UA Cohort SNCA PD Cohort SNCA UA Cohort PD Registry UA Registry TOTAL

8 LUMBAR PUNCTURE COMPLETENESS Group Baseline # Expected (% Comp) 6 Months # Expected (% Comp) 1 Year #Expected (% Comp) 2 Year #Expected (% Comp) 3 Year #Expected (% Comp) 4 Year #Expected (% Comp) PD 423 (98%) 391 (88%) 393 (84%) 336 (82%) 155 (81%) 32 (72%) HC 196 (97%) 183 (87%) 185 (84%) 161 (80%) 126 (80%) 24 (79%) SWEDD 64 (92%) 55 (85%) 58 (83%) 49 (76%) N/A N/A Hyposmic 22 (91%) 10 (70%) 5 (60%) N/A N/A N/A RBD 37 (92%) 22 (91%) 4 (75%) N/A N/A N/A Genetic PD 69 (90%) 3 (100%) N/A N/A N/A N/A Genetic UA 54 (93%) 8 (50%) N/A N/A N/A N/A 8

9 PPMI Imaging Studies In-house at IND Core Lab SPECT Scans Received: 1909 PD Year 1: 380 PD Year 2: 329 Prodromal Screening: 322 AV PET Received: Baseline: 30 Year 1: 19 Year 2: 9 (added if needed) Structural MRI Baseline: 464 (includes 78 from the prodromal cohort) DTI Baseline: 317 (includes 31 prodromal) DTI Year 1: 224 DTI Year 2: 139 Resting State: 224 As of 11 May

10 Athens Banner Barcelona Baylor Beth Israel Boca Boston Cincinnati Cleveland Clinic Columbia Emory IND Innsbruck Johns Hopkins Kassel London Macquarie Northwestern Norway OHSU Paris Pennsylvania Rochester Salerno San Sebastian Tel Aviv The PI Tuebingen UAB UCSD UCSF USF Washington Number of Kits Study Visits with Samples at Biorepository First Quarter study visits Site

11 Data Flow Clinical data sent to LONI from CTCC weekly Biorepository Imaging data Genetics - Reconciliation of different data streams

12 Requirements for Biomarker Infrastructure Parkinson s Progression Markers Initiative Specific Data Set Appropriate population (early stage PD and controls) Clinical (motor/non-motor) and imaging data Corresponding biologic samples (DNA, blood, CSF) Standardization Uniform collection of data and samples Uniform storage of data and samples Strict quality control/quality assurance Access/Sharing Data available to research community data mining, hypothesis generation & testing Samples available for studies 12

13 Standardization of data acquisition/analysis Training Matrix Training/Re-training Clinical data entry. Biosample collection and shipping UPDRS Neuropsych Imaging acquisition and data transfer Genetics Quality control of biosamples, imaging data

14 Requirements for Biomarker Infrastructure Parkinson s Progression Markers Initiative Specific Data Set Appropriate population (early stage PD and controls) Clinical (motor/non-motor) and imaging data Corresponding biologic samples (DNA, blood, CSF) Standardization Uniform collection of data and samples Uniform storage of data and samples Strict quality control/quality assurance Access/Sharing Data available to research community data mining, hypothesis generation & testing Samples available for studies 14

15 PPMI Data Sharing

16 Standardization of data acquisition/analysis Succeeded New stuff always adding Avaialbel and cllaoboartcollabortivr Subjects there Data subsets Publications Gneeteics Phenoconversion Assays Plans for future - funding, clincial studies, new assesmsneet s OPDN at

17 PPMI funding partners PPMI is sponsored and partially funded by The Michael J. Fox Foundation for Parkinson s Research. Other funding partners include a consortium of industry players, non-profit organizations and private individuals.

18 PPMI SC and Study Cores

19 PPMI SC and Study Cores Steering Committee Clinical Coordination Core Imaging Core Statistics Core Bioinformatics Core BioRepository PI-K Marek, C Tanner, T Foroud, D Jennings, K Kieburtz, W Poewe, B Mollenhauer, T Simuni, D Galasko (core leaders, MJFF, ISAB), S Lasch University of Rochester s Clinical Trials Coordination Center PI: Karl Kieburtz, Ray Dorsey, Renee Wilson Institute for Neurodegenerative Disorders; PI: John Seibyl, Norbert Schuff, University of Iowa PI: Chris Coffey Laboratory of Neuroimaging (LONI) at UCLA PI: Arthur Toga, Karen Crawford Indiana University/Biorep/Tel Aviv PI: Tatiana Foroud Biofluid Genetics Core RBD Core Olfactory Core Genetics Coordinating Core PI: Brit Mollenhauer, Doug Galasko, John Trojanowski, Les Shaw National Institute on Aging/NIH PI: Andy Singleton Hephata Hessisches Diakoniezentrum e. V. PI: Geert Mayer Institute for Neurodegenerative Disorders PI: Danna Jennings Indiana University PI: Tatiana Foroud

20 PPMI MJFF team Sohini Chowdhury, PPMI Overall Project Manager Mark Frasier, Katie Kopil - Biologics (Biorepository selection; biologic collection SOPs, assay identification and optimization) Vanessa Arnedo, Katie Forsberg, Alyssa Reimer - Recruitment/Retention Strategies, Contracting Jamie Eberling - Imaging Core and imaging SOPs Todd Sherer - MJFF CEO Debi Brooks, Industry partnership development, Media Strategies 20

21 PPMI Committees Biologics Brit Mollenhauer Doug Galasko Imaging John Seibyl Norbert Schuff Neuropsych /Neurobehavior Dan Weintraub Sleep Wolfgang Oertel Genetics Andrew Singleton LRRK2 Tatiana Foroud Susan Bressman Statistical Chris Coffey ISAB Jesse Cedarbaum Biospecimen review Kalpana Merchant Data and publication David Standaert Ancillary study Carlie Tanner Recruitment/Retention Danna Jennings Patient Advisory Danna Jennings Ken Marek Website Carlie Tanner CSOC Ron Pfeiffer 21

22 PPMI SITES IN THE UNITED STATES: Arizona PD Consortium (Sun City, AZ) Beth Israel Medical Center (NY, NY) Baylor College of Medicine (Houston, TX) Boston University (Boston, MA) Cleveland Clinic (Cleveland, OH) Columbia University (NY, NY) Emory University (Atlanta, GA) Institute of Neurodegenerative Disorders (New Haven, CT) Johns Hopkins University (Baltimore,MD) Northwestern University (Chicago, IL) Oregon Health and Science University (Portland, OR) The Parkinson s Institute (Sunnyvale, CA) PD & Movement Disorders Center at Boca Raton (Boca Raton, FL) University of Alabama at Birmingham (Birmingham, AL) University of California at San Diego (San Diego, CA) University of California at San Francisco (San Francisco, CA) University of Cincinnati (Cincinnati, OH) University of Pennsylvania (Philadelphia, PA) University of Rochester (Rochester, NY) University of South Florida (Tampa, FL) University of Washington (Seattle, WA) PPMI Sites PPMI SITES IN EUROPE: Foundation for Biomedical Research of the Academy of Athens (Athens, Greece) Imperial College (London, UK) Innsbruck University (Innsbruck, Austria) Norwegian University of Science and Technology (Trondheim, Norway) Paracelsus-Elena Clinic Kassel/University of Marburg (Kassel and Marburg, Germany) Pitié-Salpêtrière Hospital (Paris, France) University of Barcelona (Barcelona, Spain) University of Donostia (San Sebastien, Spain) University of Salerno (Salerno, Italy) University of Tübingen (Tübingen, Germany) PPMI SITES IN AUSTRALIA: Macquarie University (Sydney, Australia) PPMI SITES IN Israel: Tel Aviv Sourasky Medical Center (Tel Aviv, Israel)

23 PPMI MILESTONES ADD DTI ADD SWEDD Complete PD/HV ENROLLMENT PRODROMAL ADD AMYLOID ENROLLMENT GENETIC 2500 LPs Complete PRODROMAL 2000 DaTscan 370,000 DOWNLOADS 50 BRC applications ENROLLMENT PD/HV 1000 subjects 1000 WRI 40 PUBLICATION

24 Meeting Goals Review study success Growth of PPMI data set Continued outstanding retention Clinical, Imaging, biospecimen assessments as per protocol compliance and standardization PPMI infrastructure - biorepository transition Data and Specimen sharing New cohort and ancillary studies added

25 Meeting Goals Identify study challenges Subject Retention Longitudinal assessment Enroll Genetic cohort Data Quality PPMI fatigue Increase industry sponsorship

26 Meeting Goals Plan PPMI future iterative study - Novel analytes, imaging tools, clinical assessments, analyses Focus on PPMI data analyses longitudinal data, PD subsets, prodromal data Develop tools for Prodromal assessments Phenoconversion Focus on genetic enrollment/retention Implement pathology core Longterm PPMI follow-up How can PPMI inform clinical trials

27 PPMI Annual Meeting Agenda 2015 Day 1

28 PPMI Annual Meeting Agenda 2015-Day 1

29 PPMI Annual Meeting Agenda Day 2

30 PPMI Annual Meeting Agenda Day 2