Frontiers Clinical and Translational Science Unit

1. Frontiers Clinical and Translational Science Unit Jeffrey M. Burns, MD, MS Edward H. Hashinger Associate Professor of Neurology Director, Clinical and Translational Science Unit

2. What is the CTSU? • Clinical and Translational Science Unit • NIH-Funded • A program of Frontiers: Heartland Institute of Clinical and Translational Research • The new GCRC • Main unit is in the new Clinical Research Center • CTSU satellite • CTSU without walls program

3. What is the CTSU? • Supports research activity • Physical Infrastructure • Clinic rooms • Infusion center • Exercise physiology • Sleep lab and beds for extended stays • Metabolic kitchen • Nursing • Coordinators • Recruitment Program • Registry • Pioneers Community Registry • CTSU Satellite / CTSU Without Walls program

4. KU Clinical Research Center http://www.youtube.com/watch?v=zsMBazY31S0

5. Clinical Space • 17 exam rooms for multi-purpose outpatient testing • 2 Cognitive testing rooms • 2 Isolation exam rooms, designed for smoking cessation studies or infectious disease studies • 2 clinical rooms with observation capability via a one-way window • Workspace for up to 8 study coordinators to set up for the day while in the CTSU

6. Infusion Center • 11 infusion suites for drug administration and pharmacokinetic studies • Investigational pharmacy in the Clinical Research Center • Nursing support

7. Sample Processing Lab • Refrigerated centrifuges • Microcentrifuge • YSI glucose analyzer • -80 freezers for short or long term specimen storage • -20 freezer and refrigerator • Dry Ice

8. KU Alzheimer’s Disease Center

9. A National NIA-Designated Alzheimer’s Disease Center • Build and develop regional AD and brain aging research programs • We conduct and enable all types of AD research • World leader in AD/age-related brain energy metabolism research • Research infrastructure organized by “Cores” • Clinical Core with 400 carefully characterized subjects

10. KU ADC Integration with the CTSU Space • Clinical Evaluations • Cognitive Testing Nursing • Blood draws • Study Drug Infusions • Glucose Tolerance Tests • Clamp Procedures

11. Safety and Tolerability of R(+) Pramipexole in Alzheimer’s Disease (SPA) • Study of safety of (R+) pramipexole in AD • Antioxidant; being tested in ALS • No Placebo • 6 month treatment period • Biomarker assessments (CSF) • FDG PET • Cognitive testing

12. Alzheimer’s Disease Neuroimaging Initiative-2 (ADNI-2) • Evaluate clinical and “biomarker” parameters in control, MCI, AD subjects • Cognitive testing • Imaging (MRI, FDG PET, amyloid PET) • Genetic (blood) • Biomarkers (blood, CSF) • Longitudinal (4.5 years) • Observational (no intervention)

13. Exercise Physiology Laboratory • Exercise Physiologist, ACSM Certified • Maximal Graded Exercise Testing with Medical Monitoring • Two Parvo Medics Metabolic Carts • Physical Function Testing • Quantitative Muscle Assessment • EMG and Nerve Conduction Studies

14. Exercise Physiology Laboratory • Pulmonary Function Testing • Quantitative Sensory Testing • Doppler Ultrasound • Multiple Modalities and Protocols • Treadmill • Cycle • Recumbent Stepper • Upper Body Ergometer • 2 DEXA scanners • Body composition , bone density

15. Exercise Physiology Laboratory 2 Dexa Scanners • Prodigy DPX • iDXA • Advanced Adipose Imaging

16. Exercise Physiology Laboratory • Exercise Training Interventions • Resistance (Weight) Training • Treadmill Training

17. Exercise Physiology Laboratory QSART + Tilt Table • Autonomic Function Testing (WR Medical) • QSART: quantitative sudomotor axon reflex test, sympathetic cholinergic function • Reflexive cardiovagal function: eg. Heart rate response to deep breathing • Reflexive sympathoneural function • Orthostatic intolerance

18. Extended Observation Unit / Sleep Lab • Extended Observation Unit (EOU) to allow evening stays • 3 hospital-style suites • Study drug administration, observation & PK lab draws • Sleep Program opened in October 2012 (Suzanne Stevens)

19. Metabolic and Demonstration Kitchens • Assessment of dietary intake • Direct or digital photograph observation • 24-hour recalls • Food records • Food frequency questionnaires • Screeners • Nutrition interventions • Recipe Development and Testing • Research diets / Controlled feeding protocols • Standardized meals

20. KU ADC Integration with the CTSU Space • Clinical Evaluations • Cognitive Testing Nursing • Blood draws • Study Drug Infusions • Glucose Tolerance Tests • Clamp Procedures Exercise Physiology • Physical function testing • Maximal Exercise Testing • DEXA • Resistance exercise training Demonstration Kitchen • Healthy Cooking Class

21. Physical Activity Exercise and fitness Diet / Metabolism Insulin / glucose Body composition Obesity (fat-mass), muscle mass Mental Activity Brain Aging Project:The role of lifestyle factors in brain aging and Alzheimer’s disease Brain Atrophy Vascular Changes Markers of Alzheimer’s

22. Cardiorespiratory Fitness:Oxygen Consumption

23. Higher Physical Fitness is Associated with Less Brain Atrophy Fitness associated with less atrophy in brain areas most affected by AD Fitness Level Burns et al, Neurology, 2008 Honea et al, Alz Dis Assoc Dis, 2009

24. Lean Mass in AD • Lower lean mass in AD • Associated with brain atrophy and cognition Burns et al, Archives Neurology 2010

25. Bone Density and Bone Loss in AD Baseline Bone Density 2-yr Bone Loss p=0.02 Loskutova et al., JAD, 2009

26. Trial of Resistance Training Increased Alzheimer’s Susceptibility (TORTIAS) Does Building Muscle Build Brain? • A study of weight lifting for people without memory problems • Eligible: 55-75 years olds who aren’t weight lifting • Commitment: 2 hours/week for 12 weeks • What do we measure before and after exercise? • Brain structure (MRI) • Brain function (fMRI) • Muscle mass

27. Insulin for Memory (INFORM) • Evaluate insulin resistance-memory relationships • One 6 hour visit • hyperinsulinemic-euglycemic clamp (tests insulin resistance) • memory testing • DEXA scan (defines body composition)

28. CTSU without Walls • CTSU Satellite • Clinical space on main campus (Delp) • Mobile nurses • Research Coordinators

29. Research Coordinator Pool Service • $60 per hour or % FTE • Contract with PI for services • Coordinator may provide services including • Regulatory processing for the trial • Coordinating and conducting study visits • Performing study-required procedures • Documentation • Assisting with monitor visits • Many other tasks and duties

30. Clinic in the CTSU • December 2012: 6 rooms will be dedicated to support clinical activity • Clinicians who are doing research in the CTSU can host clinic in the CTSU

31. Participant Recruitment • Research Participant Registry • Pioneers program

32. Research Participant Registry Program • Comprehensive registry of KUMC patients willing to be contacted for participation in research studies • 4 clinics started in 2009, now active 17 clinics • 13,206 enrolled in registry by September 2012 • 17 researchers have received contact information for 25 protocols (7 PhDs, 8 MDs, 1 PharmD and 1 MSPT) • 148 participants identified from the registry have been enrolled in protocols

33. Pioneers Community Registry • Web-based Community Registry • PI: Patricia Kluding, PhD • Branding, website development ongoing • Single sign-up process • Open to all Frontiers investigators • Powerful search options with EMR access • No cost to investigators to manage database, search for participants • Able to screen with study-specific questions

34. Become a Pioneer! • Electronic informed consent form • Email verification • Brief redcap survey: • Demographic and contact info • Medical history info (self report) • Option to link to EMR if KUMC patient • Can register self, children, family member / surrogate

35. Summary of CTSU • The purpose of the CTSU is to support research by providing • Space • Nursing / coordinators • Access to important resources • Exercise physiology • Overnight stay and sleep lab capabilities • Metabolic kitchen • Recruitment tools • Frontiers Registry, Pioneers Program

36. CTSU Charges • Room rate (Minimum 1 hr. fee) 12.50/hr. • Vital Signs, Height, Weight 12.50/hr. • Phlebotomy 12.50/hr. • Specimen processing 12.50/hr. • Spirometry 50.00 • Glucose Tolerance Test 100.00 • Pregnancy Test 5.00 • EKG 35.00 • Skin caliper test 5.00

37. CTSU Charges Medication Administration • Infusion Charge 87.50 • PO, SC or IM 25.00 • Physical Exam MD/NP 100.00 Exercise Physiology Testing • Exercise Physiologist Support 37.50/hr. Dexa • Hip/spine/forearm 50.00 • Total body 50.00

38. CTSU Charges Exercise Tests • Submaximal test 75.00 • Submaximal or max w/ EKG 100.00 • Metabolic cart / resting metabolic rate 50.00 Ultrasound blood flow measures 75.00/subject 50.00/subject for device only • Conference Room 25.00/hr • Demonstration Kitchen 100.00/hr

39. Contact Us • Jeffrey Burns, MD, Director, CTSU • 913-588-0073, Jburns2@kumc.edu • Patricia Kluding, PhD, Associate Director, CTSU • 913-588-6918, pkluding@kumc.edu • Jo Denton, RN, MSN, CCRC, Administrative Director, CTSU • 913-588-0046, jdenton@kumc.edu www.frontiersresearch.org