Motivating Occupational Virtual Experiences In Therapy for Kids (MOVE-IT)
Phase: NA
Conditions: Virtual Reality, Occupational Therapy
Sponsor: Barron Associates, Inc.

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Motivating Occupational Virtual Experiences In Therapy 
(MOVE-IT) Phase II 
 
 
 
Sponsor: Barron Associates, Inc.  
 
 
Funding Mechanism: NIH SBIR Grant with Subcontract to UVA 
 
 
Principal Investigator: Richard Stevenson, M.D. 
 
 
Version Number:5.0 
                                                         08/14/2023

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i 

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i 

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i 
 
 
 
Statement of Compliance 
The study will be carried out in accordance with Good Clinical Practice (GCP) as required by the following: 
• 
U.S. Code of Federal Regulations applicable to clinical studies (45 CFR 46) 
• 
ICH GCP E6 
• 
Completion of Human Subjects Protection Training 

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SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments and provides the necessary assurances that this 
trial will be conducted according to all stipulations of the protocol, including all statements regarding confidentiality, and according to 
local legal and regulatory requirements and applicable US federal regulations and ICH guidelines. 
 
Principal Investigator:  
 
Signed: 
 
Date: 
 
 
Richard Stevenson, M.D. 
 
 
 

 
Table of Contents 
 
 
page 
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iii 
Statement of Compliance ............................................................................................................... i 
Signature Page ............................................................................................................................. ii 
List of Abbreviations ..................................................................................................................... iv 
Protocol Summary ..................................................................................................................... …v 
1 
Key Roles ............................................................................................................................. 1 
2 
Background Information and Scientific Rationale ................................................................ 2 
2.1 
Background Information ........................................................................................... 2 
2.2 
Scientific Rationale ................................................................................................... 4 
2.3 
Potential Risks and Benefits ..................................................................................... 5 
2.3.1 
Potential Risks .............................................................................................. 5 
2.3.2 
Known Potential Benefits .............................................................................. 6 
3 
Objectives ............................................................................................................................ 7 
4 
Study Design ........................................................................................................................ 8 
5 
Study Population .................................................................................................................. 9 
5.1 
Selection of the Study Population ............................................................................ 9 
5.2 
Inclusion/Exclusion Criteria ...................................................................................... 9 
5.3 
Subject Compensation ........................................................................................... 10 
6 
Study Procedures/Evaluations ........................................................................................... 12 
6.1 
Study Procedures ................................................................................................... 12 
6.2 
Laboratory Evaluations ........................................................................................... 17 
7 
Statistical Considerations ................................................................................................... 18 
7.1 
Study Outcome Measures ...................................................................................... 18 
7.2 
Sample Size Considerations .................................................................................. 18 
7.3 
Participant Enrollment and Follow-Up .................................................................... 18 
7.4 
Analysis Plan .......................................................................................................... 19 
8 
Subject Confidentiality ........................................................................................................ 21 
9 
Informed Consent ............................................................................................................... 23 
10 
Data and Safety Monitoring Plan-IRB-HSR to serve as sIRB of Record ........................... 25 
10.1 
Definitions ............................................................................................................... 25 
10.1.1 How will you define adverse events (AE)? ................................................. 25 
10.1.2 How will you define an unanticipated problem? ......................................... 25 
10.1.3 What are the definitions of a protocol deviation and/or noncompliance? ... 26 
10.2 
What risks are expected due to the intervention in this protocol? .......................... 26 

DMID Minimal Risk – One Blood Draw Protocol Template 
Version 1.0 
 
27 February 2004 
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Table of Contents - continued 
 
 
page 
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10.3 
When will recording and reporting of unanticipated problems/adverse events begin? 
27 
10.4 
When will the recording/reporting of unanticipated problems/adverse events end?27 
10.5 
What is your plan for safety monitoring? ................................................................ 27 
10.6 
What is your plan for reporting an Unanticipated Problem, Protocol Deviations or Data Breach? 
28 
10.6.1 Reporting Requirements for UVA Site ........................................................ 28 
10.6.2 Reporting Requirements for the non-UVA site(s) ....................................... 30 
11 
Literature References ......................................................................................................... 32 
 
 

List of Abbreviations 
 
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v 
AE 
Adverse Event 
CFCS 
Communication Functional Classification System 
CFR 
Code of Federal Regulations 
CHAMP 
Children with Hemiparesis Arm and Movement Project 
CIMT 
Constraint Induced Movement Therapy 
CRF 
Case Report Form 
CSA 
Combined Statistical Area 
DSMB 
Data and Safety Monitoring Board 
FDA 
Food and Drug Administration  
FWA 
Federal-Wide Assurance 
GCP 
Good Clinical Practice 
HEP 
Home Exercise Program 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
JTHFT 
Jebsen Taylor Hand Function Test  
MOVE-IT  
Motivating Occupational Virtual Experiences In Therapy  
MSA 
Metropolitan Statistical Area 
N 
Number (typically refers to subjects) 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QUEST 
Quality of Upper Extremity Skills Test  
RCT 
Randomized Controlled Trial 
SAE 
Serious Adverse Event 
SUS 
System Usability Scale 
TAM 
Technology acceptance model  
UCT 
Usual Care Treatment  

DMID Specimen Protocol Template: Minimal Risk 
Version 5.0 
 
14 August, 2023 
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DRAFT 
 
List of Abbreviations - continued 
 
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UE 
upper extremity 
UVA  
University of Virginia  
WMFT 
Wolf Motor Function Test 
 

 
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Protocol Summary 
Title: 
Motivating Occupational Virtual Experiences In Therapy (MOVE-IT) Phase II  
 
Sites: 
University of Virginia (Charlottesville, VA) and Duke University (Durham, NC) 
 
Sponsor: 
Barron Associates, Inc. (Charlottesville, VA) 
 
Study Design:  
Rater-blinded randomized controlled study 
 
Population: 
N:  
 
48 Dyads* (24 at each of 2 sites) 
 
 
 
 
*Dyad=One parent/legal guardian and one minor 
 
Ages: 
 
4 – 14 years (inclusive) 
 
Sex: 
 
Any 
 
Race: 
 
Any 
 
Diagnosis:  
Hemiplegia resulting from cerebral palsy, stroke, or other form of brain injury 
Recruitment area: Charlottesville Metropolitan Statistical Area (MSA), Raleigh-Durham-Chapel Hill Combined Statistical Area (CSA), 
and surrounding areas.  
 
Subject Duration: 10-week intervention with 3 months follow up assessment. 
 
Study Duration: 
Approximately 1 year 
 
Objectives: 
 The primary Phase II investigational objective is to show a differential effect on the pre-to-post-intervention change in upper extremity 
(UE) motor function between an interventional group receiving the MOVE-IT home exercise program (HEP) and a usual care treatment 
(UCT) group, as assessed by the Jebsen Taylor Hand Function Test (JTHFT) and other gold-standard clinical assessments of UE function. 

 
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 Blinded assessors, certified for the study instruments, will evaluate children in both groups at pre-treatment (baseline), immediate 
post-treatment (baseline + 10 weeks), and 3 months post-treatment. Assessments (3 total) will take place in an outpatient setting and 
include the following blinded instruments: 
• Jebsen Taylor Hand Function Test (JTHFT) (primary outcome measure) 
• Quality of Upper Extremity Skills Test (QUEST) (dissociated movements and grasp components) 
• Wolf Motor Function Test (WMFT) 
Additionally, parents will be asked to complete the following parental report instrument during each assessment visit: 
• Pediatric Motor Activity Log (inventory of child’s functional use of the UE) 
  For both groups, parents will be asked to maintain a weekly activity log, including activities

 
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1 
KEY ROLES 
Study Principal Investigator and Medical Expert:   Richard Stevenson, M.D.  
(UVA Primary Contact) 
 
Address: 
UVA Developmental Pediatrics 
Battle Building 
1204 W. Main St. 
Charlottesville, VA 22903 
Email:   
rds8z@hscmail.mcc.virginia.edu 
 
 
 
 
 
 
Duke Site Principal Investigator:   
Robert Lark, MD  
(Duke Primary Contact) 
 
Address: 
Duke University Health System 
Department of Orthopedics 
3000 Erwin Rd,  
Durham, NC 27705 
Email:   
robert.lark@duke.edu 
 
Study Coordinator:   
 
Abbey Adeyemo 
 
 
 
 
 
UVA Children’s Hospital  
                                                                  Email: rre2av@uvahealth.org  
 
 
Study Biostatistician:  
 
James T. Patrie, M.S. 
 
 
 
 
 
UVA School of Medicine  
Email:   
jp4h@embarqmail.com 
 

 
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2 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE  
2.1 
Background Information  
  Virtual worlds-based games present a unique, innovative, and timely solution for supporting high-dosage evidence-based 
rehabilitation that targets neuroplasticity. There exists a substantial body of work on adaptations of VR for adult rehabilitation, much 
of which has focused on stroke [31], [32], [33], [34]. Studies involving children have not kept pace with adult applications and pediatric 
applications of VR have been relegated primarily to the academic realm. Preliminary results have shown some promise, both in terms 
of patient engagement and efficacy, but prior research lacks well-powered RCTs and has not been translated to clinical practice [35], 
[36], [37], [38], [39], [40], [41].  
  Barron Associates, Inc. (the NIH grantee for the MOVE-IT program) previously developed the Virtual Occupational Therapy Application 
(VOTA), an FDA-cleared software system that enables adult stroke patients to re-learn adult activities of daily living (ADLs), such as 
shopping or meal preparation, by practicing the physical movements within a virtual environment that reconstructs real-world tasks 
[42], [43] with Kinect-based human motion capture. VOTA has been shown to improve UE function in adult stroke patients [44], [45] 
and is now sold commercially as SaeboVR [46]. 
  The MOVE-IT system, developed by Barron Associates, Inc. under NIH sponsorship, employs therapy games that combine virtual- and 
real-world physical elements to provide a solution suitable for both home use. MOVE-IT engages patients in repetitive practice, 
facilitating an evidence-based approach that integrates proven concepts in CIMT.  MOVE-IT system consists of a multi-sensory smart 
toy (which serves as a game controller), a depth camera (e.g. Kinect), a personal computer, and a virtual world software application 
with mini- games designed to sustain engagement in remotely monitored home-based therapy. Software includes mini-games such as 
Feeding Time and Flight School (shown in Figure 1) that are designed to support mass practice of UE reaching movement involving the 
shoulder, elbow, and hand. For example, in Feeding Time the player uses the smart toy to capture dragon food and bring it to the 
hungry baby dragon. Each movement to capture the food and then bring it to the dragon requires a point-to-point UE reaching 
movement. Target positioning for these reaching movements (the food and the dragon) is designed to elicit a specific degree of 
movement, determined by participating pediatric rehabilitation doctors and OTs, and categorized by difficulty and movement type to 
permit tailoring of the game for the individual patient. Note that the avatar’s arm in the game moves according to the sensor-derived 
arm joint angles, not hand position. This has the important effect of making level of difficulty for a given movement invariant to the 
child’s arm length (a 4-year-old and 14-year-old will experience that same challenge in reaching the food and feeding the dragon). As 

 
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another example, the Flight School mini-game is designed to challenge the child’s range of motion in forearm supination, an important 
movement in therapy for pediatric hemiplegia. The game translates the player’s pronation/supination movements into left-right 
steering of the baby dragon’s flight. The player uses these movements to steer the dragon through a series of targets to gain speed 
and collect rewards.  
 
Figure 1. MOVE-IT system in use during Phase I pilot testing 
  The NIH-sponsored MOVE-IT Phase II program culminates in a rater-blinded randomized, controlled trial to investigate efficacy of a 
MOVE-IT based intervention in home use by children with hemiplegia, as measured by change in gold-standard measures of UE 

 
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function for a cohort using MOVE-IT compared to a usual care treatment (UCT) group. The University of Virginia (UVA) will serve as 
coordinating center and single IRB (sIRB) for a two-site MOVE-IT RCT that includes UVA and Duke University. Overall direction of the 
RCT will be provided by Dr. Richard Stevenson, M.D., Head, Division of Developmental Pediatrics, UVA School of Medicine and former 
President of the American Academy for Cerebral Palsy and Developmental Medicine. Participation of the Duke University site will be 
under the direction of pediatric rehabilitation specialist Dr. Robert Lark, M.D. 
2.2 
Scientific Rationale  
  Hemiplegia is a partial paralysis or weakness of one side of the body that impairs the use of the UE on the affected side and disrupts 
motor functions essential to self-care, play, exploratory learning, and daily activities. Causes of pediatric hemiplegia encompass any 
injury or illness associated with the brain, including cerebral palsy (CP), cerebral vascular accident (stroke), traumatic brain injury, 
brain tumor, or other illness [1]. CP impacts more than 1 in 300 children, with disproportionate prevalence in minority and 
economically disadvantaged populations [2]. Prevalence of CP has been reported to be 50-100% higher among black or African 
American children than other demographics [3]. Overall, 60% of children with CP experience some level of impairment in UE function 
[4], which can include reduced range of motion (e.g. in the shoulder in the frontal plane [5] and in forearm pronation/supination [6]) 
and the presence of significant compensatory movement (especially of the trunk). Stroke is a form of acquired brain injury caused by 
an occlusion or rupture of blood vessels [1]. Although more commonly associated with adults, stroke impacts individuals of all ages, 
including children [7].  
  Usual care for pediatric hemiplegia includes occupational therapy (OT) as well as adjunct therapies, such as spasticity-reducing 
medications. These approaches to upper-limb therapy can be considered effective to the extent they improve independence and a 
child’s ability to meet individual goals [8].  
  Systematic reviews strongly support that constraint-induced movement therapy (CIMT) is one of the most effective treatments for 
pediatric hemiplegia [9], [10], [11], [12], [13], [14]. In CIMT, the less affected UE is constrained (i.e. typically employing a cast or mitt) 
while the impaired limb is engaged in intensive, repetitive, activity-based training [15], [16]. When considering alternate approaches, 
higher duration of training is consistently associated with better outcomes [17], [18], [8]. Meta-analysis examining 42 randomized and 
controlled trials involving UE interventions (n = 1454 subjects) found moderate to strong evidence supporting the superiority of 
intensive, task-directed training over usual care [19]. These regimes are associated with superior outcomes in spontaneous use, quality 
of movement, and task performance [20], [21]. 

 
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  Neuroplasticity provides one possible explanation for why increased dosage/intensity produces superior outcomes over usual care. 
Brain plasticity can be defined as the formation of new circuits and changes to internal structures that remap existing synapses to 
perform functions previously accomplished by injured cortical tissue [22], [23]. Although the relationship between therapy for 
pediatric hemiplegia and brain neuroplasticity is only beginning to be understood, emerging evidence appears to mirror findings in 
stroke research that frequent, longer-duration interventions improve cortical activation and neuroplasticity, and thus lead to better 
outcomes [24], [25]. Functional MRI results appear to show that intensive training can produce neuroplastic changes on the synaptic 
level in children with CP, evidenced by increased task-related brain activation in the lesioned region of the primary motor cortex [26], 
[27], [28].  
  New intensive therapy regimes strain the capacity and resources of delivery systems and challenge the creativity of individual 
therapists to maintain patient engagement and motivation. Total dosages for CIMT in clinical trials have involved up to 126 hours of 
therapist-supervised training [20]. A study comparing efficacy of 30 vs. 60 hours of CIMT for children with unilateral CP found 60 hours 
to be sufficient, but 30 insufficient, to achieve desired outcomes [29]. When reducing CIMT dosage to numbers more typical for usual 
care, outcomes fall short compared to more intensive training [29]. It thus appears that 50-60 hours are needed in clinical practice 
[30], but delivering such dosages strains the capacity of existing health systems and can exceed the reimbursement limits of insurers. 
Using delivery mechanisms typical of usual care, a 1-to-1 child-to-therapist ratio may be required to achieve adequate dosage [29]. 
Individual therapists also face the formidable challenge of keeping patients motivated in more frequent and longer practice sessions.  
2.3 
Potential Risks and Benefits 
2.3.1 Potential Risks 
   Potential risks are described below, along with mitigation measures that will be implemented by the study team. 
(1) 
Soreness, pain, or increased tone post-use due to increased range and level of activity involving the upper extremity. 
a. Game-integrated movements will be consistent with accepted clinical practice for occupational therapy and exercises used 
in previous RCTs involving intensive therapy (e.g. the CHAMP R01 program RCT, NCT01895660.);  
b. Subjects will be reminded to take frequent breaks.  
c. Study staff will ensure families understand that they can withdraw from the study at any time without reason or 
consequence.  
d. At least once every two weeks, study staff will contact the participant by phone or HIPAA compliant video conferencing to 
collect self-reported adherence data and confirm that no change in medical status has occurred that would impact 

 
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continued participation.  The staff member will inquire regarding soreness, pain, or increased tone and consult with the PI 
if any concerns are reported.  
(2) Elevated stress or embarrassment due to frustration with the interface or inability to perform a task.  
a. Initial visits with licensed pediatric therapists assesses appropriateness of MOVE-IT use for the individual patient and the 
home environment; 
b. Physical and cognitive demands are progressive and appropriate for the participant population and consistent with existing 
clinical practice; and  
c. At least once every two weeks, study staff will contact the participant by phone or HIPAA compliant video conferencing. If 
elevated stress, embarrassment, or frustration are reported, a study pediatric therapists will adjust the activity settings and 
follow up with the parent or guardian to ensure the issue is resolved. If the issue cannot be resolved to the satisfaction of 
the therapist and parent, the PI will be consulted regarding appropriateness of continued participation.  
(3) Risk of accidental release of identifying and/or confidential information. 
a. Potential risks of accidental release of identifying and/or confidential information will be mitigated by use of a coded 
identifier key for all participant data and implementation of detailed measures described in the Data Security Plan.  
2.3.2 Known Potential Benefits 
Potential benefits to participants in this study will include the opportunity to learn about the potential benefits of new 
technology and gaming for improving upper extremity function in children with hemiplegia. The knowledge gained from this 
study may lead to substantial benefits for both individuals (in improving motor function and functional independence) and 
society (by increasing access to and reducing the cost of care). Subjects assigned to the MOVE-IT HEP group may benefit from 
participation by improved UE motor status. Subjects assigned to the UCT group will be offered access to the MOVE-IT HEP 
following completion of participation as a control. 

 
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3 
OBJECTIVES 
  The primary Phase II investigational objective is to show a differential effect on the pre-to-post-intervention change in upper 
extremity (UE) motor function between an interventional group receiving the MOVE-IT home exercise program (HEP) and a usual 
care treatment (UCT) group, as assessed by the Jebsen Taylor Hand Function Test (JTHFT) and other gold-standard clinical 
assessments of UE function. 
  Blinded assessors, certified for the study instruments, will evaluate children in both groups at pre-treatment (baseline), immediate 
post-treatment (baseline + 10 weeks), and 3 months post-treatment. Assessments (3 total) will take place in an outpatient setting and 
include the following blinded instruments: 
• Jebsen Taylor Hand Function Test (JTHFT) (primary outcome measure) 
• Quality of Upper Extremity Skills Test (QUEST) (dissociated movements and grasp components) 
• Wolf Motor Function Test (WMFT) 
  Additionally, parents will be asked to complete the following parental report instrument during each assessment visit: 
• Pediatric Motor Activity Log (inventory of child’s functional use of the UE) 
  For both groups, parents will be asked to maintain a weekly activity log, including activities performed under the MOVE-IT 
intervention and any other therapy a child might receive. 
 

 
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4 
STUDY DESIGN 
  The study is a randomized control study. 
 
  Following screening, enrolled subjects will be randomized to either the MOVE-IT home exercise program (HEP) or usual care 
treatment (UCT) group using a centralized and masked process developed by the study biostatistician. The HEP group is the 
interventional group. The UCT group is the control group. Following the control strategy previously adopted in the Children with 
Hemiparesis Arm and Movement Project (CHAMP) multi-site RCT (NICHD R01, trial registration number NCT01895660), children in 
the UCT group will be followed as they continue to receive their previously prescribed therapy services. As UCT group participants, 
these children will not receive any treatment services through the study. Parents will be asked to report therapy services their 
children receive during each assessment visit. 
 
  To ensure that an approximately equal number of subjects are randomized to the MOVE-IT HEP and UCT groups throughout the 
Phase II enrollment period, we will randomly assign the patients to the two study-groups in accordance with a permuted block 
randomization scheme. The randomization list will be generated by a UVA study biostatistician (James Patrie) using the  PLAN 
procedure of SAS (SAS Institute Inc., Cary, NC).  One subject randomization table will be generated for each site.  The group 
assignment will be blinded to the therapists (raters) who perform the pre- and post-assessments. The group assignment will be not 
be blinded to the participants. The non-rater members of the IRB-approved study team will have access to the randomization list. 
 
  Demonstration of statistically significant improvement in UE motor function for participants the MOVE-IT HEP versus UCT will 
support the validity of MOVE-IT use as an intervention for children with hemiplegia. In home use, MOVE-IT will enable more 
frequent and intensive therapy with reduced travel and may extend the service range of existing rehabilitation providers to include 
underserved areas. In clinical practice, MOVE-IT will enable new models of delivery based on remote monitoring combined with 
outpatient services, increasing quality and efficiency of care. Statistical considerations for sample size determination, primary 
analysis, and secondary analyses are described below.  
 
 

 
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5 
STUDY POPULATION 
5.1 
Selection of the Study Population 
 
Ages:  
4 – 14 years (inclusive) 
Sex: 
 
Any 
Race:  
Any          
 
Target # of subjects (at all sites) needed to complete protocol: 40. 
Expected rate of screen failure/ dropouts/withdrawals from all sites: 15%.  
Number of subject/dyads to be enrolled at all sites: 48.  
Number of subjects who will sign a consent form under this protocol: 48 dyads.  
(24 at UVA and 24 at Duke) 
5.2 
Inclusion/Exclusion Criteria 
Criteria for inclusion  
(1) Diagnosis of hemiplegia resulting from cerebral palsy, stroke, or other form of brain injury; 
(2) Medically stable; 
(3) Manual Abilities Classification System (MACS) rating between II and V; indicating the child experiences mild to severe 
difficulty in handling objects with the affected hand;  
(4) Communication Functional Classification System (CFCS) rating between I and III; indicating the child usually communicates 
effectively with familiar communication partners, but not unfamiliar partners, in most environments; 
(5) Participant has antigravity strength in the affected UE at the elbow to at least 45 degrees of active flexion; 
(6) Participant has antigravity shoulder strength in the affected UE to at least 30 degrees each in active flexion, 
abduction/adduction, and 15 degrees in active internal/external rotation when in an upright and seated position; 
(7) Participant has ability to perform a basic color-matching test and identify characters on a vision chart; 

 
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10 
(8) Participant must be available to attend study visits;  
(9) Willingness and ability to comply with scheduled visits and study procedures. 
 
Criteria for exclusion 
(1) History of uncontrolled seizures; 
(2) Has received botulinum toxin injections, stem cell infusions or another form of intensive UE therapy, such as CIMT, within 
the prior 6 months; 
(3) Unwillingness or inability to understand or follow verbal directions; 
(4) Diagnosis of moderate to severe cortical-visual impairment that in the judgement of the Principal Investigator could 
adversely impact the subject’s participation; 
(5) Psychological diagnosis that in the determination of the Principal Investigator could significantly impact subject’s 
participation or that could be aggravated by study participation; 
(6) Determination that participation would result in over exertion, or significant discomfort or pain; 
(7) Determination that participation would result in significant agitation or elevated stress; 
(8) Visual field deficit in either eye that impairs the ability to view the computer monitor. 
 
Restrictions on use of other drugs or treatments: None 
5.3 
Subject Compensation 
Participants will be compensated for being in this study.  
Participants will be paid a $50 stipend for each outpatient visit completed (3 total visits). Participants will not be compensated 
for home visits. 
If a participant drops out or is otherwise disenrolled form the study, payments will be pro-rated based on number of visits 
completed ($50 per outpatient visit).  
Participants will not receive reimbursement for actual expenses related to being in this study (e.g. travel).  

 
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6 
STUDY PROCEDURES/EVALUATIONS 
6.1 
Study Procedures 
  Identical procedures will be followed at the UVA and Duke sites.  
 
  Prior to consent, candidates will be contacted by phone and the parent/guardian asked to respond to questions pertaining to eligibility 
(inclusion/exclusion criteria). For example: 
• 
Does the child have a history of uncontrolled seizures? 
• 
Has the child received botulinum toxin injections, stem cell infusions or another form of intensive arm therapy, such as CIMT, within the 
prior 6 months? 
• 
Can the child move the affected arm and flex the elbow about halfway? 
• 
Is the child’s corrected vision good enough to comfortably watch a TV show for 30 minutes? 
The final list of questions will be included in a telephone recruitment scripts that will be submitted for IRB approval prior to use. After pre-
screening using the IRB-approved script, candidates will be scheduled for a remotely-administered consent and screening telehealth visit and for 
a pre-assessment visit.  
 
- 
The parent/guardian will be asked to complete the following parental report instrument: 
o Pediatric Motor Activity Log (inventory of child’s functional use of the UE) 
 
ALL - Outpatient Visit 1: Pre-Assessment (will last about 90 minutes) 
- 
Blinded study therapist will review consent and re-verify inclusion and exclusion criteria 
- 
Blinded study therapist will administer clinical tests for UE function 
o Jebsen Taylor Hand Function Test (JTHFT) (primary outcome measure) 
o Quality of Upper Extremity Skills Test (QUEST) (dissociated movements and grasp components) 
o Wolf Motor Function Test (WMFT) 

 
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- 
If administration of the test instruments cannot be completed for any reason (e.g. subject becomes fatigued), the participants 
may be asked to return for an additional visit to complete the procedures.  The participant will be provided the normal per-visit 
stipend for the additional visit.  
- 
Subject will be assigned to either the MOVE-IT HEP or the UCT group employing the study randomization procedure and 
scheduled for remaining visits.  
 
GROUP 1: MOVE-IT HEP GROUP  
 
MOVE-IT HEP Visit 1 (will last about 90 minutes) 
- 
A non-blinded study team member will conduct a home visit at the patient’s residence. 
- 
The team member will either drop off the system with the family OR set up the MOVE-IT system in the home and verify 
safety of the system setup. 
- 
A therapist will guide the patient in practice using the MOVE-IT system either in-person at the home or via approved 
telehealth connection.  The therapist will provide training to the parent/guardian either in-person in the home or via 
approved telehealth connection. 
MOVE-IT HEP Home Visit 2 (will last about 60 minutes) 
- 
A non-blinded study therapist will conduct a second home visit at the patient’s residence or meet with the subject via 
approved telehealth connection. 
- 
The therapist will observe the patient in practice using the MOVE-IT system and provide additional guidance and training 
as needed. 
- 
If on the study therapist’s recommendation, the study PI determines an additional visit is warranted to ensure a patient 
can safely and successfully use the system at home, an additional visit will be conducted either in the home or via an 
approved telehealth connection.  
MOVE-IT HEP Independent Practice at Home  
- 
Participants will be asked to employ the GRASP system for UE practice at home for a total of 1 hour/day, 5 days/week 
over the 10-week intervention period.  
- 
Patients will continue to perform any previously prescribed therapy.  

 
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14 
- 
Once per week during this period, non-blinded study staff will employ an authorized web application on a UVA computing 
system to remotely monitor de-identified participant data (see Data Security Plan for details) that includes exercise 
adherence (duration performed), movement repetitions accomplished (exercise reps), and exercise intensity (speed).  
- 
At least once every two weeks, non-blinded study staff will contact the participant by phone or HIPAA compliant video 
conferencing to collect self-reported adherence data and confirm that no change in medical status has occurred that 
would impact continued participation.  
 
MOVE-IT HEP Home Visit 3 (will last about 90 minutes)  
- 
At the end of the HEP period, a non-blinded team member will conduct a home visit at the patient’s residence to recover 
the system hardware.  Prior to recovery, a therapist will observe patients’ independent use of the system either in the 
home or via an approved telehealth connection. 
- 
Participants will respond to usability assessment instruments including: 
o System Usability Scale (SUS) 
o Technology acceptance model (TAM) questionnaire 
o Short response open-ended narrative questions.  
These assessments will be audio recorded using Zoom. The recordings will be stored in secure folders on O/drive at UVA 
and Duke Box, that only the research team has access to. The interview recording will only identify subjects with their 
subject ID. Transcriptions will be reviewed by a member of the research team for accuracy. Once reviewed and 
transcribed, all identifiable information will be removed and only the de-identified transcript will be stored and used for 
analysis. Another member of the research team will perform a quality check of the transcript to ensure accuracy.  
 
GROUP 2: UCT GROUP: 
- 
Participants in the control group will continue to receive any previously prescribed therapy services. These patients will 
not receive any treatment services through the study as UCT group participants.  
- 
At least once every two weeks during the interventional period, non-blinded study staff will contact the participant by 
phone or HIPAA compliant video conferencing to collect self-reported adherence data and confirm that no change in 
medical status has occurred that would impact continued participation.  
 

 
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15 
ALL - Outpatient Visit 2: Post-Assessment (will last about 90 minutes) 
- 
Conducted at end of 10-week intervention period.  
- 
Blinded study therapist will administer the same battery of tests used in pre-assessment.  
 
ALL - Outpatient Visit 3: Follow-up Assessment (will last about 90 minutes) 
- 
Conducted approximately 3 months after Post-Assessment.  
- 
Blinded study therapist will administer the same battery of tests used in pre- and post-assessment.  
 
To promote equipoise, parents of children in the UCT group will be provided free access to the MOVE-IT HEP following completion of 
the control protocol. When participation in the study is completed, all subjects will return to usual care under their individual health 
care provider.  
 
A graphical summary of the MOVE-IT Phase II study is provided in Figure 2 below.  
 
 

 
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16 
 
Figure 2. MOVE-IT Phase II Study Plan 
 

 
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17 
6.2 
Laboratory Evaluations 
No laboratory evaluations will be conducted under this study.  

 
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18 
7 
STATISTICAL CONSIDERATIONS 
7.1 
Study Outcome Measures 
7.2 
Sample Size Considerations 
  Power analysis for the study is based on approximate effect size and variance information derived from previous RCTs involving 
intensive therapy for children with hemiplegia. In particular, JTHF outcomes reported by Klingels et al. provide approximate effect 
size and variance. For the Wilcoxon Mann-Whitney test, if 20 subjects per group (40 total) complete the protocol, we will have at 
least 0.80 power (<0.05) if the true underlying probability that the MOVE-IT pre-to-post intervention change in JTHFT score is 
greater than the pre-to-post change for UCT is 0.75 or greater. Recruitment of 24 subjects per group will allow a conservative 15% 
dropout rate (e.g. compared to the CHAMP R01 program RCT, NCT01895660), which assumed 10%).  
7.3 
Participant Enrollment and Follow-Up 
  Approximately 24 subjects will be recruited at each of the two sites (48 total). Recruited children will have a diagnosis of hemiplegia 
resulting from cerebral palsy, stroke, or other form of brain injury; be between 4 and 14 years of age; have no history of uncontrolled 
seizures; and be medically stable. Children will be excluded if they received botulinum toxin injections, stem cell infusions or another 
form of intensive UE therapy, such as CIMT, within the prior 6 months. Children may receive other forms of treatment or intervention 
during and after the MOVE-IT intervention; data about such other interventions will be collected prospectively from parents.  
  It is expected that participant enrollment in the MOVE-IT Phase II RCT will be open for a period of approximately 10 months. Monthly 
enrollment is projected to average from 6-12 new subjects per month across both sites. Each subject’s participation includes a 10-
week interventional (or control) period and a 3-month follow-up assessment.  
  An approximately equal number of subjects will be recruited at the UVA Children’s Hospital (n=24) and the Duke Children’s Hospital 
(n=24) study sites, facilitated by experienced study coordinators at each site. Based on recent completion of studies of similar scope, 
including the CHAMP CIMT trials at UVA [12], the team anticipates being able to meet the MOVE-IT RCT goals.  
 

 
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19 
 
7.4 
Analysis Plan 
  Primary variable analysis involves analysis of completion times for each of the seven tasks in the JTHFT which will be summed to 
produce a total score. The pre-intervention scores will be subtracted from the post-intervention scores to produce a set of delta 
values. These delta values scores (Δ) will be analyzed via Analysis of Covariance (ANCOVA). One null hypothesis will test if the mean 
pre-to-post-intervention change in the total JTHFT score is equal to zero, while the second null hypothesis will test if the mean pre- 
to post-intervention change in the JTHFT score is the same for patients who participate in a 10-week MOVE-IT HEP and patients who 
under UCT over the same duration. For both null hypotheses, a p≤0.05 decision rule will be utilized as the rejection criterion. 
Analysis of data from the 3-month follow-up assessment will be performed in a similar manner. 
  Secondary variable analysis includes analysis of the pre-to-post intervention changes in the composite WMFT scores which will be 
analyzed in the same way as the pre-to-post intervention change in the composite JTHFT scores. The same method of analysis will be 
used to analyze the pre-to-post intervention changes in the QUEST scores. 
  The Likert scale responses to the SUS questionnaire will be summarized per question, and per question category, by frequencies 
and percentages. As an overall measure of system usability, a composite SUS score in the range from 0 to 100 will be derived from 
individual responses. By convention, a SUS score greater than or equal to 68 is indicative of an efficient, effective, and satisfying 
system. For the TAM questionnaire, percentages of favorable responses to the questions of each topic will be estimated via a 
binomial generalized estimating equation model, and a 90% confidence interval constructed. A Wald test will be used to test the null 
hypothesis that the odds of a favorable response are independent of the question topic.  
  Therapy session adherence and activity will be assessed by way of a binomial generalized estimating equation model, in which 
therapy adherence and activity measures (collected via parental logs) will be compared between the patients who participate in a 
10-week MOVE-IT HEP and patients under UCT over the same duration.  
  All biostatistical design and analysis will be conducted by Mr. James Patrie, a Pstat accredited Senior Biostatistician within the 
Department of Public Health Sciences of the University of Virginia School of Medicine.  
  Data from the UVA and Duke sites will be combined during analysis. Randomization will be done at each site. Variation between the 
two sites is expected to be minimal. The effect of the treatment to be tested is expected to be the same among the two sites, which 

 
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20 
will use identical protocols.  
 

 
 _____________________________________________________________________________________________  
21 
8 
SUBJECT CONFIDENTIALITY  
  Subject confidentiality is held strictly in trust by the participating investigators, their staff, the sponsor, and their agents. The study 
protocol, documentation, data, and all other information generated will be held in strict confidence.  No information concerning the 
study, or the data will be released to any unauthorized third party without prior written approval of the sponsor. The clinical study 
site will permit access to appropriate documents and records that may require inspection by the sponsor or its authorized 
representatives including de-identified study data. 
  Only IRB-registered protocol staff will have access to the actual identities of the participants, which will remain anonymous to all 
non-IRB authorized persons. 
The sources of human research data will include the following. 
1. Demographic information, including age, sex, race, and ethnicity. 
2. Results of screening instruments. 
3. Rater-blinded assessment instruments including: JTHFT, QUEST, and WMFT. 
4. Parental report instrument Pediatric Motor Activity Log. 
5. MOVE-IT game-derived measures including achieved therapy duration, and functional movement repetitions. 
6. Weekly activity logs 
7. SUS and TAM usability questionnaires 
8. Transcribed usability data including think-aloud expressions during system use; captured in digital video, screen captures, and 
therapist notes. 
  Potential risks of accidental release of identifying and/or confidential information will be mitigated by use of a de-identified coded 
key for all subject data. The cipher that relates participants to the key will exist in hard (paper) copy only and be stored in a locked 
cabinet in a controlled-access room at the study sites. All data sheets will be properly controlled and shredded prior to disposal.  
  De-identified data covering primary and secondary measures will be analyzed by the study biostatistician. The de-identified data and 
the results of biostatistical analysis will be provided to the sponsor via encrypted means. Results will be reported by the sponsor to 
the NIH via annual and final progress reports, and incorporated into one or more manuscripts to be submitted for publication in 

 
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22 
medical journals and/or conference proceedings accessible via PubMed Central.  The MOVE-IT RCT will be registered with 
ClinicalTrials.gov and results information will be submitted according to ClinicalTrials.gov timelines.  

 
 _____________________________________________________________________________________________  
23 
9 
INFORMED CONSENT 
  The informed consent process includes parental or legal guardian permission and child verbal assent. All permission and assent 
forms will be approved by the IRB. Initial prescreening will be conducted by telephone to determine if a candidate meets basic 
enrollment criteria including age, diagnosis, and general health status. The parent or guardian of individuals passing phone 
prescreening will be provided a read-ahead copy of the permission and assent forms. The forms will include a summary of the study 
protocols, details on inclusion and exclusion criteria, and details on exercise components. Candidates will subsequently be scheduled 
for an initial consent and screening visit.  
  During the administration of the permission and assent process, trained study staff will provide the parent or guardian and child an 
informational overview, verbally guide them through the permission form, provide a summary for each section and ask for verbal 
confirmation of understanding of each section. The parent will then be given an opportunity to read the entire form, or have the form 
read to them if they are unable or prefer not to read it themselves. The study therapist will then verify understanding by asking the 
following question: “If you were to explain what is happening in this study to a family member or friend, what would you say to them?” 
If the parent or guardian is unable to demonstrate understanding, the study therapist will re-review the permission form and repeat 
the question. Individuals will be informed of the ability to withdraw from the study at any time and for any reason with no negative 
consequence.  
  If the parent or guardian demonstrates understanding of the protocol, he/she will be given the opportunity to sign the permission 
form. The child will then be given the opportunity to provide assent. The child will be provided with a summary of the study and give 
the opportunity to demonstrate his or her understanding and willingness to participate. If permission and assent are provided, the 
parent or guardian will be provided a copy of the signed forms. The original will be filed in the secure study file.  
 
Consent Visit (in-person or remotely administered, will last about 45 minutes) 
- 
The child and a parent/guardian will take part in remotely-administered telehealth visit with a study coordinator or a study 
therapist by phone or HIPAA compliant video conferencing (e.g. Zoom Health) OR take part in-person. 
- 
Participants will be asked pre-screening questions to verify inclusion and exclusion criteria. 
- 
Participants at the University of Virginia will complete informed consent and assent using DocuSign or alternative institutionally-
approved method.  

 
 _____________________________________________________________________________________________  
24 
- 
Participants at Duke University will complete informed consent and assent using a wet signature if the consenting meetings takes 
place in-person, such as in clinic.  If the consenting process takes place via HIPAA compliant video conferencing or phone, study 
staff will direct the parent/guardian to sign the consent in the appropriate spaces.   Study staff will then provide a mailing 
address for the participant to send the completed consent form.  Duke study staff will document the reason remote consent was 
obtained (i.e. in-person consent not possible due to distance from Duke University).  
 

 
 _____________________________________________________________________________________________  
25 
10 
DATA AND SAFETY MONITORING PLAN-IRB-HSR TO SERVE AS SIRB OF 
RECORD 
This study has been deemed minimal risk.  Because this study poses minimal risk to the subject, adverse events will only be 
collected or recorded if a causal relationship to the study intervention is suspected.  If any adverse event is considered serious and 
unexpected, the event must be reported to the IRB-HSR within 7 days from the time the study team receives knowledge of the 
event.  
 
10.1 Definitions 
10.1.1 How will you define adverse events (AE)? 
Do not change this answer 
An adverse event will be considered any undesirable sign, symptom or medical condition considered related to the 
intervention. Medical condition/diseases present before starting the intervention will be considered adverse events 
only if they worsen after starting the study and that worsening is considered to be related to the study intervention.  
An adverse event is also any undesirable and unintended effect of research occurring in human subjects as a result of 
the collection of identifiable private information under the research.   
 
10.1.2 How will you define an unanticipated problem?  
Do not change this answer 
An unanticipated problem is any issue that involves increased risk(s) 
to participants or others.  This means issues or problems that cause the subject or others to be placed at greater risk 
than previously identified, even if the subject or others do not incur actual harm.  For example if a subject’s 

 
 _____________________________________________________________________________________________  
26 
confidentiality is compromised resulting in serious negative social, legal or economic ramifications, an unanticipated 
problem would need to be reported. (e.g. serious loss of social status, loss of job, interpersonal conflict.)     
 
10.1.3 What are the definitions of a protocol deviation and/or noncompliance?  
Do not change this answer 
A protocol deviation is defined as any change, deviation, or departure from the study design or procedures of research 
project that is NOT approved by the IRB-HSR prior to its initiation or implementation.  Protocol deviations may be 
major or minor.   
 
Noncompliance can be a protocol deviation OR deviation from standard operating procedures, Good Clinical Practices 
(GCPs), federal, state or local regulations.   Noncompliance may be minor or sporadic, or it may be serious or continuing. 
 
Additional Information: see the IRB-HSR website at  
Protocol Deviations, Non-compliance and Protocol Exceptions  
 
10.2 What risks are expected due to the intervention in this protocol?   
Expected Risks related to study participation 
Pick One 
There is a small risk that breaches of privacy and/or 
confidentiality might occur. The risk of violation of subject 
privacy and confidentiality is minimal due to the requirements 
of the privacy plan in this protocol.  
Occurs rarely 
There is a minor risk that soreness, pain, or increased tone 
may occur post-use due to increased range and level of 
activity involving the upper extremity. The risk is minor as 
game-integrated movements are consistent with accepted 
Occurs rarely 

 
 _____________________________________________________________________________________________  
27 
clinical practice and exercises used in previous RCTs involving 
similar therapy (e.g. the CHAMP R01 RCT, [12]).   
There is a minor risk of elevated stress or embarrassment due 
to frustration with the interface or inability to perform a task. 
The risk is minor as cognitive demands are progressive and 
appropriate for the participant population and consistent with 
existing clinical practice. Study pediatric therapists will tailor 
the activities to the capabilities of the patient.   
Occurs rarely 
 
10.3 When will recording and reporting of unanticipated problems/adverse events begin? 
__x___After subject begins study intervention 
 
10.4 When will the recording/reporting of unanticipated problems/adverse events end?  
___x__Subject completes participation in the protocol 
 
10.5 What is your plan for safety monitoring?   
Do not change this answer 
Safety monitoring and aggregate review of adverse events, unanticipated problems, protocol violations and any data breach will be 
performed by the PI and IRB-HSR through continuation review at least annually.   
 

 
 _____________________________________________________________________________________________  
28 
10.6 What is your plan for reporting an Unanticipated Problem, Protocol Deviations or Data 
Breach?  
 
10.6.1 Reporting Requirements for UVA Site 
Type of Event 
To whom will it be 
reported: 
Time Frame for 
Reporting 
How reported? 
Unanticipated Problems that 
are not adverse events or 
protocol deviations  
This might include a Data 
Breach.   
IRB-HSR 
 
 
Within 7 calendar 
days from the time 
the study team 
received knowledge 
of the event.  
Unanticipated Problem report form.  
 
Unanticipated Problem Report Form 
 
Protocol 
Deviations/Noncompliance 
(The IRB-HSR only requires that
MAJOR deviations be reported,
unless otherwise required by 
your sponsor, if applicable.) 
 
 
IRB-HSR 
 
 
Within 7 calendar 
days from the time 
the study team 
received knowledge 
of the event.  
 
Protocol Deviation, Noncompliance and Protocol Exception 
Reporting Form 
 
Protocol Deviation Protocol Exception Reporting Form 
 
 
 

 
 _____________________________________________________________________________________________  
29 
Data Breach* of Protected 
Health Information  
 
 
 
The UVa Corporate 
Compliance and 
Privacy Office 
 
 
ITC:  if breach 
involves  electronic 
data  
 
 
 
 
Police if breach 
includes items that 
are stolen: 
 
Stolen on UVA 
Grounds 
 
OR  
 
Stolen off UVa 
Grounds- contact 
police department of 
jurisdiction of last 
known location of 
PHI 
As soon as possible 
and no later than 24 
hours from the time 
the incident is 
identified. 
 
As soon as possible 
and no later than 24 
hours from the time 
the incident is 
identified. 
 
 
IMMEDIATELY.  
 
UVa Corporate Compliance and Privacy Office- Phone 924-9741 
 
 
 
 
ITC:  Information Security Incident Reporting procedure,  
https://security.virginia.edu/report-information-security-incident 
 
 
 
 
 
 
Police: phone- (434) 924-7166 
*A data breach is defined in the HITECH Act (43 USC 17932) as an unauthorized acquisition, access, or use of protected 
health information (PHI) that compromises the security or privacy of such information. 
Additional Information may be found on the IRB-HSR Website: Data Breach 
 
 

 
 _____________________________________________________________________________________________  
30 
10.6.2 Reporting Requirements for the non-UVA site(s) 
 
Type of Event 
To whom will it be 
reported: 
Time Frame for 
Reporting 
 
How reported? 
 
Unanticipated Problems that are not 
adverse events or protocol deviations  
This might include a Data Breach.   
UVA study team/ Data 
Coordinating Center 
 
UVA lead site or DCC 
will report to the IRB-
HSR  per table above 
 
 
Within 7 calendar 
days from the 
time the study 
team received 
knowledge of the 
event.  
Written documentation.   
 
May use the Relying Site Unanticipated Problem Reporting 
Form 
Protocol Deviations/Noncompliance 
The IRB-HSR only requires that MAJOR 
deviations be reported, unless otherwise 
required by your sponsor, if applicable. 
 
OR 
 
Protocol Exceptions 
See definition- only allowed if there is a 
commercial sponsor or a DSMB that has 
granted the protocol exception.  
UVA study team/ Data 
Coordinating Center 
 
UVA lead site or DCC 
will report to the IRB-
HSR per table above 
 
Within 7 calendar 
days from the 
time the study 
team received 
knowledge of the 
event.  
 
 
Written documentation.   
 
May use the Relying Site Protocol Deviation/Exception 
Reporting Form 

 
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31 
Data Breach  
Per local relying 
institution 
requirements 
 
The UVA IRB-HSR only 
needs to be notified of 
any data breach that 
meets the criteria of a 
UP 
Per local relying 
institution 
requirements 
 
Per local relying institution requirements. 
 
 

 
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32 
11 
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