AWARD NUMBER: W81XWH-16-1-0726 TITLE: A Randmized Cntrlled Trial f the Grup-Based Mdified Stry Memry Technique in TBI PRINCIPAL INVESTIGATOR: Nancy D. Chiaravallti, PhD CONTRACTING ORGANIZATION: Kessler Fundatin West Orange, NJ 07052 REPORT DATE: Octber 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Cmmand Frt Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Apprved fr Public Release; Distributin Unlimited The views, pinins and/r findings cntained in this reprt are thse f the authr(s) and shuld nt be cnstrued as an fficial Department f the Army psitin, plicy r decisin unless s designated by ther dcumentatin.
REPORT DOCUMENTATION PAGE Frm Apprved OMB N. 0704-0188 Public reprting burden fr this cllectin f infrmatin is estimated t average 1 hur per respnse, including the time fr reviewing instructins, searching existing data surces, gathering and maintaining the data needed, and cmpleting and reviewing this cllectin f infrmatin. Send cmments regarding this burden estimate r any ther aspect f this cllectin f infrmatin, including suggestins fr reducing this burden t Department f Defense, Washingtn Headquarters Services, Directrate fr Infrmatin Operatins and Reprts (0704-0188), 1215 Jeffersn Davis Highway, Suite 1204, Arlingtn, VA 22202-4302. Respndents shuld be aware that ntwithstanding any ther prvisin f law, n persn shall be subject t any penalty fr failing t cmply with a cllectin f infrmatin if it des nt display a currently valid OMB cntrl number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE Octber 2017 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2016-29 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Randmized Cntrlled Trial f the Grup-Based Mdified Stry Memry Technique in TBI 5b. GRANT NUMBER W81XWH-16-1-0726 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Nancy D. Chiaravallti, PhD 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail:nchiaravallti@kesslerfundatin.rg 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) KESSLER FOUNDATION INC 120 Eagle Rck Avenue Suite 100 East Hanver, NJ 07936 5f. WORK UNIT NUMBER 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR S ACRONYM(S) U.S. Army Medical Research and Materiel Cmmand Frt Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT Apprved fr Public Release; Distributin Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Impairments in new learning and memry (NLM) are cmmn deficits in individuals with Traumatic Brain Injury (TBI) and exert significant negative impact n everyday life. There is thus a need fr effective interventins fr learning and memry dysfunctin in TBI, particularly grup-based interventins fr which 3 rd party payment may be mre frthcming, The current study addresses this need thrugh a duble blind, placeb-cntrlled, randmized clinical trial (RCT) f a grup administratin f the mdified Stry Memry Technique (msmt). Over a decade f research and develpment at ur center has demnstrated the msmt t be effective fr imprving NLM in individuals with Multiple Sclersis (MS) and TBI acrss three realms f functining, bjective behavir, brain functining and everyday life. This cnvincing data prvides Class I evidence supprting the efficacy f the msmt fr imprving NLM in these ppulatins. Given the strng efficacy data n the msmt, cupled with the current trends in insurance reimbursement, clinicians wrldwide have highlighted the need t prvide the msmt via an effective grup frmat. We have thus mdified the treatment prtcl fr grup administratin. This pilt 15. SUBJECT TERMS Memry, TBI, cgnitin, cgnitive rehabilitatin, cgnitive retraining, new learning, treatment 16. SECURITY CLASSIFICATION OF: U a. REPORT U Unclassified b. ABSTRACT U Unclassified c. THIS PAGE U Unclassified 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES UU Unclassified 11 19a. NAME OF RESPONSIBLE PERSON USAMRMC 19b. TELEPHONE NUMBER (include area cde) Standard Frm 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18
Table f Cntents Page 1. Intrductin.1 2. Keywrds.1 3. Accmplishments.....1 4. Impact... 6 5. Changes/Prblems.... 6 6. Prducts....7 7. Participants & Other Cllabrating Organizatins 7 8. Special Reprting Requirements 9 9. Appendices 9
1. INTRODUCTION: Impairments in new learning and memry are amng the mst cmmn deficits in individuals with Traumatic Brain Injury (TBI) and have been shwn t exert significant negative impact n everyday life. There is thus a tremendus need fr the develpment f effective interventins fr learning and memry dysfunctin in TBI, particularly grup-based interventins fr which 3 rd party payment may be mre frthcming, The current study addresses this critical need thrugh the cnduct f a duble blind, placeb-cntrlled, randmized clinical trial (RCT) f a grup administratin f the mdified Stry Memry Technique (msmt). Over a decade f research and develpment cnducted at ur center has demnstrated the msmt t be effective fr imprving new learning and memry in individuals with Multiple Sclersis (MS) and TBI acrss three realms f functining, bjective behavir, brain functining and everyday life. This cnvincing data prvides Class I evidence supprting the efficacy f the msmt fr imprving new learning and memry in these ppulatins. Given the strng efficacy data n the msmt, cupled with the current trends in insurance reimbursement, clinicians wrldwide have highlighted the need t prvide the msmt via an effective grup frmat. We have thus mdified the treatment prtcl fr grup administratin. This pilt RCT tests the efficacy f a grup administratin f the msmt fr persns with mderate t severe TBI. 2. KEYWORDS: Prvide a brief list f keywrds (limit t 20 wrds). Memry, TBI, cgnitin, cgnitive rehabilitatin, cgnitive retraining, new learning, treatment 3. ACCOMPLISHMENTS: What were the majr gals f the prject? The current study addresses the fllwing specific aims. Aim 1. Objectively evaluate the efficacy f the grup msmt t imprve new learning/memry in individuals with TBI with dcumented deficits in this area. Aim 2. Increase the generalizability and real life applicatin f the grup msmt by assessing utcme fllwing grup msmt with glbal measures f everyday life, including ne bjective measure and multiple subjective measures. Aim 3. Examine the neurfunctinal changes resulting frm the grup-based msmt in TBI subjects with impairments in new learning and memry. We will examine if neurfunctinal changes in the brain are assciated with behaviral imprvements fllwing the msmt and if these changes are maintained ver time. Aim 4: Evaluate the lng-term efficacy f the grup msmt thrugh a 3-mnth fllw-up. T accmplish these aims, the fllwing majr tasks were identified: Majr Task 1: Administratively Prepare fr Clinical Trial Target cmpletin date: 1/1/17 Actual cmpletin date: 1/1/17 Percent f cmpletin: 100% 4
Majr Task 2: Crdinate Study Staff fr Clinical Trial Target cmpletin date: 4/1/17 Actual cmpletin date: 4/1/17 Percent f cmpletin: 100% Majr Task 3: Prepare Research Prtcl Target cmpletin date: 2/1/17 Actual cmpletin date: 2/1/17 Percent f cmpletin: 100% Majr Task 4: Participant Recruitment, Treatment, Participant Evaluatin Target cmpletin date: 9/30/19 Actual cmpletin date: n/a Percent f cmpletin: 40% (6 participants f 15 targeted) Majr Task 5: Data Analysis Target cmpletin date: 9/30/19 Actual cmpletin date: n/a Percent f cmpletin: n/a What was accmplished under these gals? 1) Majr Activities: Deadline Status Majr Task 1: Administratively Prepare fr Clinical Trial 1/1/17 cmplete Majr Task 2: Crdinate Study Staff fr Clinical Trials 4/1/17 cmplete Majr Task 3: Prepare Research Prtcl 2/1/17 cmplete Majr Task 4: Participant Recruitment, Treatment, Participant Assessment 9/30/19 nging 2) Specific Objectives: Majr Task 1: Administratively Prepare fr Clinical Trial Subtask 1: Prepare Regulatry Dcuments and Research Prtcl Deadline Status Finalize cnsent frm & human subjects prtcl 1/1/17 cmplete Submit prtcl t IRB 1/1/17 cmplete Submit prtcl fr Military IRB Review (ORP/HRPO) 4/1/17 cmplete Submit amendments, adverse events and prtcl deviatins as needed As needed Crdinate with Sites fr annual IRB reprt fr cntinuing review Annually 5
Milestne Achieved: Lcal IRB apprval at KF 1/1/17 cmplete Milestne Achieved: HRPO Majr Task 2: Crdinate Study Staff fr Clinical Trials Subtask1: Hiring and Training f Study Staff Prepare jb descriptin design 11/1/16 cmplete Advertise and interview fr prject related staff 1/1/17 cmplete Crdinate fr space allcatin fr new staff 1/1/17 cmplete Train staff fr treatment and assessment activities 3/1/17 cmplete Milestne Achieved: Research staff trained 4/1/17 cmplete Subtask 2: Facilitate hiring, training, supervisin and fidelity checks as nging needed fr attritin and treatment fidelity Milestne Achieved: Maintained trained and available staff thrughut nging duratin f clinical trial Majr Task 3: Prepare Research Prtcl Finalize administratin prcedures fr grup msmt 2/1/17 cmplete Finalize assessment prcedures; assemble testing binders and testing files 2/1/17 cmplete fr NPE and AGF Ensure apprpriate prgramming f eprime stimulus delivery f 2/1/17 cmplete neurimaging stimuli Finalize timing and parameters fr the cllectin f ptimal imaging data 2/1/17 cmplete Milestne Achieved: bth utcme assessments and treatment prtcl nging finalized and running smthly Majr Task 4: Participant Recruitment, Treatment, Participant Evaluatin Subtask 1: Participant recruitment & enrllment Begin recruitment and screening f apprpriate ptential participants fr 4/1/17 cmplete study participatin Milestne Achieved: 1 st 3-5 participants cnsented, screened and 5/1/17 cmplete enrlled Milestne Achieved: First grup treatment perid cmpleted successfully 7/1/17 cmplete Recruitment and screening cntinues nging nging Participants cmplete assigned cnditin grup treatment t reach nging nging target n f 90 Cmplete fllw-up assessments 3 mnths after cmpletin f treatment nging nging Milestne Achieved: Data cllectin cmplete; data analysis begins 9/30/19 3) Significant results r key utcmes: Data cllectin is nging and has been prgressing well. We have recently encuntered slwed enrllment and we are currently brainstrming abut ways t address this. This is a very difficult study t recruit fr because individuals have t cme t Kessler fr treatment and because it is a grup treatment, their schedules need t cincide. We are currently explring the pssibility f hlding the grups ff-site at day treatment prgrams r clubhuses. There are n ther results t reprt as data cllectin is nging. 6
4) ther achievements. As summarized abve, this first grant year has been a very busy year. The first majr task was t administratively prepare fr the study. This included preparing regulatry dcuments and the research prtcl, which cnsisted f multiple time-cnsuming prcesses including preparing cnsent frms and human subjects prtcls, lcal IRB review, military IRB review, etc. This was all achieved n time. The secnd majr task was t crdinate the study staff fr the clinical trial. This is als a time-cnsuming prcessing that invlves hiring the apprpriate staff, training all staff n assessment and treatment prcedures, ensuring the adequacy f training, advertising fr the study, cmpiling all assessment and training prtcls, crdinating space allcatin, and identifying technlgical needs and capabilities. This was als all cmpleted n time. Majr Task 3 required the preparatin f the research prtcl including the treatment administratin prcedures, bth neurpsychlgical and neurimaging assessment prcedures, and timing, all f which was cmpleted n time. Finally, we were able t initiate participant recruitment, testing and enrllment. The first grup cmpleted treatment successfully and we are ready t begin the 2 nd grup nw. Recruitment has been increasingly difficult, detailed belw. We are thus explring additinal ptins fr recruitment. Recruitment details: 249 peple with mderate t severe TBI were cntacted fr ptential participatin in the study. 33 f the 249 were backgrund screened 18 didn t qualify based n backgrund screen. 15 peple qualified based n the backgrund screen 8 peple were brught in fr in-persn screen. 1 persn failed the in-persn screen 1 persn qualified based n the in-persn screen, but decided nt t participate due t the time cmmitment. 6 peple are enrlled, 4 f which cmpleted the study. 3 f these peple were cntacted multiple times t schedule in-persn screen, but never gt back. 1 persn was scheduled fr in-persn screen, cancelled appintment and isn t free t participate until 2018. 3 ther peple are nt free t participate until 2018. 57 f the 249 were nt interested due t time cmmitment r culdn t travel t us 130 f the 249 culd nt be reached after multiple attempts and did nt return ur calls 2 f the 249 mved ut f state 3 f the 249 asked t be called back in a few weeks r mnths 24 f the 249 did nt qualify based n infrmatin garnered during a casual cnversatin (e.g. had a strke rather than TBI) What pprtunities fr training and prfessinal develpment has the prject prvided? This prject was nt intended t prvide training and prfessinal develpment. Hwever, staff recruited fr the study include bachelr s level research assistants that received substantial n-the-jb training in neurpsychlgical assessment, wrking with persns with 7
TBI and the cgnitive rehabilitatin prtcl being studied. This is dne thrugh ne-n-ne wrk with a mentr and results in increased knwledge r skill in neurpsychlgical assessment and functining. All study staff additinally participate in the semi-annual TBI Cnsumer Cnference held (9/29/2017 this year) and have many pprtunities t attend lectures and wrkshps at Kessler r Rutgers University. Hw were the results disseminated t cmmunities f interest? What d yu plan t d during the next reprting perid t accmplish the gals? Gals fr the next reprting perid fcus n participant recruitment, enrllment and treatment. We will be meeting with lcal day treatment TBI prgrams t explre hlding the grups at their center. This will ease the burden f participatin fr the participants and hpefully facilitate increased recruitment. This is a bit challenging due t technlgy needs, but it shuld be pssible. We will be cntinuing t run grups at Kessler Fundatin as well and we will be wrking with ur newly hired patient recruitment specialist t increase awareness f the study in the TBI Cmmunity and hpefully referrals fr participatin. We hpe this 2-prnged apprach t recruitment, bth new appraches, serve t increase ur rate f enrllment. 4. IMPACT: What was the impact n the develpment f the principal discipline(s) f the prject? What was the impact n ther disciplines? What was the impact n technlgy transfer? What was the impact n sciety beynd science and technlgy? 5. CHANGES/PROBLEMS: While we are explring different ptins fr recruiting participants, this will nt invlve any changes t the study prtcl. All methdlgy will remain as prpsed. Changes in apprach and reasns fr change Actual r anticipated prblems r delays and actins r plans t reslve them The nly anticipated delay is the delay in recruitment that we have already encuntered and is already being addressed 8
Changes that had a significant impact n expenditures Significant changes in use r care f human subjects, vertebrate animals, bihazards, and/r select agents Significant changes in use r care f human subjects Significant changes in use r care f vertebrate animals. Significant changes in use f bihazards and/r select agents 6. PRODUCTS: 7. PARTICIPANTS & OTHER COLLABORATING ORGANIZATIONS What individuals have wrked n the prject? Nancy Chiaravallti, PhD; PI; n change Glenn Wylie, D.Phil.; c-i; n change Jhn DeLuca, PhD; c-i; n change Nancy Mre, MA; Research Manager; n change Name: Prject Rle: Nearest persn mnth wrked: Cntributin t Prject: Ekaterina Dbryakva, PhD C-investigatr (replaced Helen Genva, PhD) 5 Dr. Dbryakva prvides imaging expertise in the day t day data 9
cllectin f the functinal imaging data Funding Supprt: Natinal MS Sciety Name: Prject Rle: Nearest persn mnth wrked: Cntributin t Prject: Funding Supprt: Tiffany Chang Research Assistant 5 Ms. Chang has been invlved with participant recruitment and cnducting the baseline and fllw-up assessments Natinal MS Sciety Name: Prject Rle: Nearest persn mnth wrked: Cntributin t Prject: Funding Supprt: Dnya Green Research Assistant 4 Mr. Green has been invlved with participant recruitment and cnducting the treatment sessins NIDILRR Field Initiated grant Name: Prject Rle: Eric Stne Research Assistant Nearest persn mnth wrked: 1 Cntributin t Prject: Funding Supprt: Mr. Stne has been invlved with participant recruitment. Natinal MS Sciety and NJ Cmmissin n TBI Research Name: Michael Pellicane Prject Rle: Research Assistant 10
Nearest persn mnth wrked: Cntributin t Prject: Funding Supprt: 2 Mr. Pellicane had been invlved with participant recruitment and cnducting the treatment sessins. He has nw left the rganizatin. NIDILIRR Field Initiated grant Has there been a change in the active ther supprt f the PD/PI(s) r senir/key persnnel since the last reprting perid? Nthing t Reprt. What ther rganizatins were invlved as partners? Nne. Nthing t Reprt. 8. SPECIAL REPORTING REQUIREMENTS 9. APPENDICES: 11