Frontiers Clinical and Translational Science Unit

Jeffrey M. Burns, MD, MSEdward H. Hashinger Associate Professor of

NeurologyDirector, Clinical and Translational Science Unit

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

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

KU Clinical Research Center

http://www.youtube.com/watch?v=zsMBazY31S0

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

Infusion Center• 11 infusion suites for

drug administration and pharmacokinetic studies

• Investigational pharmacy in the Clinical Research Center

• Nursing support

Sample Processing Lab

• Refrigerated centrifuges• Microcentrifuge• YSI glucose analyzer• -80 freezers for short or

long term specimen storage

• -20 freezer and refrigerator

• Dry Ice

KU Alzheimer’s Disease Center

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

KU ADC Integration with the CTSU

Space• Clinical Evaluations• Cognitive TestingNursing• Blood draws• Study Drug Infusions• Glucose Tolerance Tests• Clamp Procedures

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

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)

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

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

Exercise Physiology Laboratory

2 Dexa ScannersProdigy DPXiDXA

Advanced Adipose Imaging

Exercise Physiology Laboratory

Exercise Training Interventions

Resistance (Weight) Training

Treadmill Training

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

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)

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

KU ADC Integration with the CTSU

Space• Clinical Evaluations• Cognitive TestingNursing• Blood draws• Study Drug Infusions• Glucose Tolerance Tests• Clamp Procedures

Exercise Physiology• Physical function testing• Maximal Exercise Testing• DEXA• Resistance exercise trainingDemonstration Kitchen• Healthy Cooking Class

Brain Atrophy

Vascular Changes

Markers of Alzheimer’s

Brain Aging Project:The role of lifestyle factors in brain aging and Alzheimer’s disease

• Physical Activity– Exercise and fitness

• Diet / Metabolism– Insulin / glucose– Body composition

• Obesity (fat-mass), muscle mass

• Mental Activity

Cardiorespiratory Fitness:Oxygen Consumption

Higher Physical Fitness is Associated with Less Brain Atrophy

Burns et al, Neurology, 2008

Fitness associated with less atrophy in brain areas most affected by AD

Honea et al, Alz Dis Assoc Dis, 2009

Fitness Level

Lean Mass in AD• Lower lean mass in AD• Associated with brain atrophy and cognition

Burns et al, Archives Neurology 2010

Bone Density and Bone Loss in AD

p=0.02

BaselineBone Density 2-yr Bone Loss

Loskutova et al., JAD, 2009

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

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)

CTSU without Walls

• CTSU Satellite– Clinical space on main campus (Delp)

• Mobile nurses• Research Coordinators

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

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

Participant Recruitment

• Research Participant Registry• Pioneers program

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

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

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

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

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

CTSU ChargesMedication 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

CTSU ChargesExercise 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

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