Brain Health and Fitness Overview



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Brain Health and Fitness Overview UNCLASSIFIED CAPT C. Douglas Forcino Director, Military Operational Medicine Research Program Chair, Joint Program Committee 5 for Military Operational Medicine US Army Medical Research and Materiel Command 24 March 2015 UNCLASSIFIED 1

DISCLAIMER The views expressed in this presentation are those of the author(s) and may not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government. UNCLASSIFIED 2

Brain Health Across the Military Lifecycle Treat Casualties TBI & PTSD treatment Reset Psychological health return-to-duty standards & criteria Human Systems Integration (Braincomputer interface) Post-Deployment Resilience training Re-Deployment Deployment/ Employment Cognitive performance optimization in the context of MOS Cognitive load Mobilization/ Pre-Deployment Training technology Resilience training Reconstitution K-12 thru Accession Cognitive accession standards Strategies to assess resilience Basic Training/Advanced Individual Training Cognitive fitness standards Cognitive and resilience training Gender-specific vulnerabilities Readiness Resilience training Leader training Measures of unit cohesion Behavioral screens Psychological Health return-toduty standards Separation Post-Military Surveillance Epidemiological studies to evaluate psychological health risks pertaining to military deployments Brain Health: The state of cognitive, psychological, and behavioral fitness which enables peak human performance through the brain s capabilities of attention, reasoning, decision making, problem solving, learning, communicating, and adapting. UNCLASSIFIED 3

PANEL MEMBERS COL Dallas Hack-Traumatic Brain Injury LTC Chessley Atchison-Environmental Sensors for Possible Concussive Events Dr. Thomas Balkin-Fatigue Management for the Soldier Dr. Raymond Genovese-Challenges for Developing New Pharmacologics for the Treatment of PTSD Mr. Michael Husband-Neurotrauma and Psychological Health Advanced Development UNCLASSIFIED 4

Traumatic Brain Injury Overview UNCLASSIFIED COL Dallas Hack Office of the Principal Assistant for Research & Technology US Army Medical Research and Materiel Command 24 March 2015 UNCLASSIFIED 5

TBI UNCLASSIFIED 6

Environmental Sensors for Possible Concussive Events UNCLASSIFIED LTC Chessley R. Atchison Office of the Principal Assistant for Research & Technology US Army Medical Research and Materiel Command 24 March 2015 UNCLASSIFIED 7

Purpose To increase understanding of environmental sensors for the detection of possible concussive events. Points Sensor Requirements (G s Measured, PSI measured, battery life, etc.) Sensor Wear (Fit & Function) Sensor Validation Algorithm Development (Math necessary to capture the data) Algorithm Validation Ultimate Goal: Dose Response Curve that predicts the probability of injury based on sensor data! UNCLASSIFIED 8

Training Examples Airborne Training Combatives Training UNCLASSIFIED 9

Training Examples Artillery Training UNCLASSIFIED 10

Fatigue Management for the Soldier UNCLASSIFIED Thomas J. Balkin, Ph.D. Behavioral Biology Branch, CMPNS, WRAIR US Army Medical Research and Materiel Command 24 March 2015 UNCLASSIFIED 11

Purpose To describe the unique need and capability for implementation of a comprehensive fatigue management system (FMS) in military operations. Points Sleep loss impacts both short-term performance/military effectiveness Sleep loss is ubiquitous in military operations Three-component military FMS will be complete within 3 years Remaining need: the platform (e.g., smartphone app?) for fielding of the FMS UNCLASSIFIED 12

UNCLASSIFIED/ Acute Sleep Loss Throughput (Percent of Baseline) Sleep Loss is characterized by brain deactivation especially in brain regions that mediate cognitive performance and alertness 72 Hours of Total Sleep Deprivation: Effect on Arithmetic Task Performance Performance deficits often result from the combined effects of sleep loss and circadian rhythm misalignment (e.g., nighttime operations) 120 100 80 60 40 - Mean Performance (N=8) 20 - Cubic Spline - Linear Regression 0 24 48 72 86 Sleep Deprivation (Hours)

UNCLASSIFIED Sleep & Self-Reported Mistakes in OIF Reported having an accident or mistake that affected the mission 14% 12% 10% 8% 6% 4% 2% 0% 4 or less 5 6 7 8 Source: MHAT V data Average hours of sleep per day UNCLASSIFIED

WRAIR Fatigue Management System Sleep Watch Actigraph Because that which cannot be measured in the field cannot be managed in the field An Armamentarium of Fatigue Countermeasures Stimulants to restore/maintain performance during sustained/continuous operations when there is little or no opportunity to sleep Sleep inducers/counteractants to enhance recuperative sleep when needed Alertness Management for Military Operations (AMMO) So that operational performance degradation can be anticipated and planned for, and informed decisions regarding dosage and timing of countermeasures can be made. Performance prediction Movement Activity (actigraphy) Sleep/Wake Scoring

The Final Product 16 Alertness Management for Military Operations Sleep Performance Prediction Model (SPM) Output Activitybased sleep/wake scoring Nap Soldiers wear wrist actigraph for weeks/months. Activity data serves as input Sleep Scoring Algorithm Output to sleep scoring algorithm, which in turn serves as input to AMMO. the results of which are displayed on the Soldiers personal technology, where different scenarios can be explored (e.g., what if I take a 30-minute nap at 1400 hrs? What will my performance capacity be at 0200 Hrs tomorrow if I don t get any sleep between now and then? How much benefit will I get from drinking a cup of coffee now, and for how long? etc.)

Challenges for Developing New Pharmacologics for the Treatment of PTSD UNCLASSIFIED Raymond F. Genovese, PhD Behavioral Biology Branch, CMPN, WRAIR US Army Medical Research and Materiel Command 24 March 2015 UNCLASSIFIED 17

Objectives Therapeutic protocols for PTSD guided by precision medicine. Advanced clinical development of PTSD medication in a military population. ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. UNCLASSIFIED 18

Unique Challenge of PTSD Drug Development Preclinical Models Gold Standard Compounds Extrapolation Analgesia Well-established nociception models (e.g., Tail-Flick Hot-Plate) that demonstrate predictive validity. e.g., Morphine Facilitated by preclinical models with predictive validity. Malaria In vitro and in vivo Parasite clearance models that demonstrate predictive validity. e.g., Chloroquine & Artesunate Facilitated by preclinical models with predictive validity. PTSD Many, but none that have, thus far, demonstrated predictive validity. Challenged by the difficulty of demonstrating preclinical efficacy. UNCLASSIFIED 19

Gaps NEEDED Not Needed New molecules or new applications of molecules demonstrating a convergence of positive data on multiple existing preclinical tests. Clinical trials targeting innovative and evidencebased approaches, novel pathways, novel applications and combination (pharmacologic and psychotherapeutic) strategies. New preclinical tests showing drive-by efficacy in a few select instances. UNCLASSIFIED 20

Opportunities and Partnerships GLP STUDIES IND Novel compound / application Phase I & 2 Clinical Trials UNCLASSIFIED 21

Objective Ability to identify Service Members who may be at higher risk for attempting suicide & interventions to prevent suicide attempts. UNCLASSIFIED 22

Suicide Prevention Initiatives Funded through the Defense Health Program and managed by the Military Operational Medicine Research Program (MOMRP), this innovative cutting-edge research aims to enhance the military s ability to quickly identify those at risk for suicide and provide effective evidence-based prevention and treatment strategies. https://www.msrc.fsu.edu/ UNCLASSIFIED 23

Continuing Needs Validated and effective training for bystander intervention. Validated and effective training for leader intervention. Self-management strategies for reducing suicidal thoughts. UNCLASSIFIED 24

Neurotrauma and Psychological Health Advanced Development UNCLASSIFIED Michael Husband PM NPH US Army Medical Research and Materiel Command 24 March 2015 UNCLASSIFIED 25

Purpose Neurotrauma and Psychological Health Project Management Office Mission: To coordinate and oversee advanced development and acquisition of medical products in Traumatic Brain Injury (TBI) and Psychological Health (PH) that will meet validated Warfighter needs through the execution of approved research, development, and acquisition (RDA) programs. Vision: Leading the development of innovative, evidence-based solutions for TBI and PH. UNCLASSIFIED 26

DoD Advanced Development Medically Ready Force S &T Proof of Concept Partnerships Intellectual Property Acquisition Strategy FDA Regulatory Management Clinical Development Verification and Validation Testing Manufacturing Valley of Death 27

Psychological Health 1. Drug Repurposing Novel molecular entities State of the Science Summit November 2015 2. Biomarker Use in diagnostics Use to assess endpoints in clinical trials Use to identify targets for intervention 3. Device Treatment of Posttraumatic Stress Disorder (PTSD): Invasive and Non-invasive Suicide prevention: Detection of dynamic risk 4. Knowledge Product Enhancing psychotherapies with medications or devices Clinical implementation UNCLASSIFIED 28

Traumatic Brain Injury 1. Drug Treatment of injury Treatment of symptoms 2. Biomarker Baseline risk Acute diagnosis Identification of potential subtypes Prognosis Use to assess endpoints in clinical trials Use to identify efficacy of treatment 3. Device Treatment of TBI: Invasive and Non-invasive Diagnostic: Aid to clinical assessment and patient management 4. Knowledge Product Standards for clinical assessment and treatment Clinical implementation UNCLASSIFIED 29

Product Life Cycle Industry Academia and Non- Profit JPC5/RAD 3 Military Operational Medicine JPC6/RAD2 Combat Casualty Care Other Government Agencies NPH PMO Advanced Development Technology Transfer Knowledge Product Drug Treatment - PH Drug Treatment - TBI Diagnostics - TBI Diagnostics - PH 6.1 6.2 6.3 6.4 6.5 Procurement TRL 1-3 Discovery TRL 4-5 Preclinical TRL 5-6 Phase I-II TRL 6-7 Phase II-III TRL 7-8 Phase III Premarket approval process (PMA) or 510(k) TRL 8-9 Production & Deployment Phase FDA Approved UNCLASSIFIED 30

It is estimated that over 2.3 Million US Service Members deployed 2001-2014 Incidence of TBI Incidence of PH Conditions 313,816 documented TBIs (2000-3QFY14) with over 80% classified as mild TBI and 9% moderate/severe TBI, 9% Unknown 1 (over 80% of TBIs are diagnosed in a non-deployed setting. TBI will remain a military concern long after withdrawal from Afghanistan. ) Mental Disorder 2000 2012: 159,107 active service members experienced 192,317 mental disorder hospitalizations. 5 2006 2009: > 50% increase (10,262 to 15,328) in hospitalizations from PTSD, alcohol abuse and dependence, adjustment disorder related to combat experience 6 The average costs for the first year of treatment for returning veterans $11,700 2 Direct medical costs and indirect costs of TBI, such as lost productivity, totaled an estimated $60 billion in the United States in 2000. 9 Average civilian hospital stay: Mild - 1 day per event; Moderate 6 to 7 days per event; Severe - 17-18 days per event. Rehabilitation length of stay average 55 days. According to the CDC, falls are the leading cause of TBI, while motor-vehicle-traffic injury is the leading cause of TBI death Death rate from CDC = 3% of all TBIs. 4 TBI is a contributing factor to a third of all injury-related deaths in the US. 8 PTSD and Major Depression 2001 2008: $4 - $6.2 billion = total cost for PTSD and depression in the first two years following redeployment 3 1.6 million total Iraq or Afghanistan veterans PTSD 11-20% of OEF/OIF Veterans have PTSD 10 Average costs for the first year of PTSD treatment for a returning veteran = $8,300 2 Suicide Beginning in 2010: second-leading cause of death for active duty service members, behind war injuries. 6 200 deaths by suicide in active duty service members in 1998, rising to 349 in 2012 7 UNCLASSIFIED 31

Questions? For additional questions after the conclusion of the conference, send an email message to usarmy.detrick.medcomusamrmc.mbx.mmpd@mail.mil UNCLASSIFIED 32