Dynamic Supported Mobility for Infants and Toddlers With Cerebral Palsy
Phase: NA
Conditions: Cerebral Palsy
Sponsor: Children's Hospital of Philadelphia

 
Template version: July 26, 2012 
Title: 
Improving the trajectory of motor development in infants and 
toddlers with cerebral palsy.  
Short Title 
Improving motor development in CP 
Drug or Device 
Name(s): 
N/A 
FDA IND 
N/A 
Regulatory Sponsor: 
 
eIRB Number 
 
Protocol Date: 
10/08/2014 
Amendment 1 Date:             02/24/2015 
Amendment 3 Date: 10/23/2017 
Amendment 2 Date:             02/03/2016 
Amendment 4 Date: 
 
Laura Prosser, PT, PhD 
The Children’s Hospital of Philadelphia 
Center for Rehabilitation 
34th street & Civic Center Boulevard 
Mailstop C02-1130 
Philadelphia , PA, 19104 
Phone 215-590-2495 
email: prosserl@email.chop.edu 
 
 
 

 
 
 
 
 
 
 
 
 
 
ii 
TABLE OF CONTENTS 
Table of Contents ................................................................................................................... ii 
Abbreviations and Definitions of Terms ............................................................................. iv 
Abstract .................................................................................................................................. v 
Table 1: Schedule of Study Procedures .............................................................................. vi 
Figure 1: Study Diagram ..................................................................................................... vii 
1 
BACKGROUND INFORMATION AND RATIONALE ....................................................................... 1 
1.1 
INTRODUCTION ..................................................................................................................................... 1 
1.2 
NAME AND DESCRIPTION OF INVESTIGATIONAL INTERVENTION .......................................................... 2 
1.3 
RELEVANT LITERATURE AND DATA ..................................................................................................... 2 
1.4 
COMPLIANCE STATEMENT .................................................................................................................... 7 
2 
STUDY OBJECTIVES .............................................................................................................................. 7 
2.1 
PRIMARY OBJECTIVES (OR AIMS) ......................................................................................................... 7 
2.2 
SECONDARY OBJECTIVE (OR AIM) ........................................................................................................ 8 
3 
INVESTIGATIONAL PLAN .................................................................................................................... 8 
3.1 
GENERAL SCHEMA OF STUDY DESIGN ................................................................................................. 8 
3.1.1 
Screening Phase .............................................................................................................................. 8 
3.1.2 
Study Treatment Phase (start of the study intervention) ................................................................. 8 
3.1.3 
Follow-up Phase .............................................................................................................................. 9 
3.2 
ALLOCATION TO TREATMENT GROUPS AND BLINDING ........................................................................ 9 
3.3 
STUDY DURATION, ENROLLMENT AND NUMBER OF SITES ................................................................. 10 
3.3.1 
Duration of Study Participation .................................................................................................... 10 
3.3.2 
Total Number of Study Sites/Total Number of Subjects Projected ................................................ 10 
3.4 
STUDY POPULATION ........................................................................................................................... 10 
3.4.1 
Inclusion Criteria .......................................................................................................................... 10 
3.4.2 
Exclusion Criteria ......................................................................................................................... 10 
4 
STUDY PROCEDURES .......................................................................................................................... 10 
4.1 
SCREENING VISIT ................................................................................................................................ 11 
4.2 
TREATMENT PHASE ............................................................................................................................ 11 
4.2.1 
Assessment sessions 1-5 ................................................................................................................ 11 
4.2.2 
Treatment sessions 1-72 ................................................................................................................ 11 
4.3 
FOLLOW-UP PHASE ............................................................................................................................. 11 
4.3.1 
Follow-up assessments (3, 6 and 12 months) ................................................................................ 11 
4.4 
SUBJECT COMPLETION/WITHDRAWAL ............................................................................................... 12 
4.4.1 
Early Termination Study Visit ....................................................................................................... 12 
4.4.2 
Make-up treatment sessions .......................................................................................................... 12 
5 
STUDY EVALUATIONS AND MEASUREMENTS ........................................................................... 12 
5.1 
SCREENING AND MONITORING EVALUATIONS AND MEASUREMENTS ................................................ 12 
5.1.1 
Medical Record Review ................................................................................................................. 12 
5.1.2 
Physical Examination .................................................................................................................... 12 
5.2 
EFFICACY EVALUATIONS .................................................................................................................... 13 
5.2.1 
Gross Motor Function Measure (GMFM) .................................................................................... 13 
5.2.2 
Secondary Outcomes ..................................................................................................................... 13 
5.2.3 
Weight ............................................................................................................................................ 13 
5.2.4 
Bayley Scales of Infant and Toddler Development, cognitive scale .............................................. 13 
5.2.5 
Family Empowerment Scale .......................................................................................................... 13 
5.2.6 
Possible video or photograph ........................................................................................................ 14 
5.3 
SAFETY EVALUATION ......................................................................................................................... 14 

 
 
 
 
 
 
 
 
 
 
iii 
6 
STATISTICAL CONSIDERATIONS .................................................................................................... 14 
6.1 
PRIMARY ENDPOINT ........................................................................................................................... 14 
6.2 
STATISTICAL METHODS ...................................................................................................................... 14 
6.2.1 
Baseline Data ................................................................................................................................ 14 
6.2.2 
Efficacy Analysis ........................................................................................................................... 14 
6.2.3 
Safety Analysis ............................................................................................................................... 15 
6.3 
SAMPLE SIZE AND POWER .................................................................................................................. 15 
7 
SAFETY MANAGEMENT ..................................................................................................................... 16 
7.1 
CLINICAL ADVERSE EVENTS .............................................................................................................. 16 
7.2 
ADVERSE EVENT REPORTING ............................................................................................................. 16 
8 
STUDY ADMINISTRATION ................................................................................................................. 16 
8.1 
TREATMENT ASSIGNMENT METHODS ................................................................................................. 16 
8.1.1 
Randomization ............................................................................................................................... 16 
8.1.2 
Blinding ......................................................................................................................................... 17 
8.2 
DATA COLLECTION AND MANAGEMENT ............................................................................................ 17 
8.3 
CONFIDENTIALITY .............................................................................................................................. 17 
8.4 
REGULATORY AND ETHICAL CONSIDERATIONS ................................................................................. 17 
8.4.1 
Data and Safety Monitoring Plan .................................................................................................. 17 
8.4.2 
Risk Assessment ............................................................................................................................. 18 
8.4.3 
Potential Benefits of Trial Participation ....................................................................................... 18 
8.4.4 
Risk-Benefit Assessment ................................................................................................................ 19 
8.5 
RECRUITMENT STRATEGY .................................................................................................................. 19 
8.6 
INFORMED CONSENT/ASSENT AND HIPAA AUTHORIZATION ............................................................ 19 
8.7 
PAYMENT TO SUBJECTS/FAMILIES ...................................................................................................... 20 
8.7.1 
Reimbursement for travel, parking and meals .............................................................................. 20 
8.7.2 
Payments to parent for time and inconvenience (i.e. compensation) ............................................ 20 
8.7.3 
Payments to subject for time, effort and inconvenience (i.e. compensation) ................................ 20 
8.7.4 
Gifts ............................................................................................................................................... 20 
9 
PUBLICATION ........................................................................................................................................ 20 
10 
REFERENCES ......................................................................................................................................... 21 
 

 
 
 
 
 
 
 
 
 
 
iv 
ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
TD: Typically developing  
 
CP: Cerebral Palsy 
 
GMFM: Gross Motor Function Measure 
 
BSID-III: Bayley Scales of Infant and Toddler Development, version III 
 
PT: Physical therapy

 
 
 
 
 
 
 
 
 
 
v 
ABSTRACT 
Context: Cerebral palsy (CP) is the most common cause of physical disability in children. 
There is a window of opportunity to reduce the degree of lifelong disability by maximizing 
motor potential during the critical early years of development.  
Objectives: 1) To determine the optimal treatment duration of a novel early mobility training 
program (dynamic supported mobility, DSM) between 6 to 24 weeks of treatment; and 2) To 
evaluate the clinical futility of this intervention compared to current rehabilitation practice. 
Study Design: Exploratory clinical trial 
Setting/Participants:  Sixty participants with, or with suspected, CP between the ages of 1-3 
years will be enrolled. All testing procedures and interventions will occur in the Center for 
Rehabilitation at CHOP on an outpatient basis. 
Study Interventions and Measures: Study participants will be randomly assigned to receive 
either dynamic supported mobility (DSM, experimental) treatment or intensity-matched 
conventional treatment. Repeated assessments of gross motor function will be performed 
during the treatment phase and at three follow-up points over one year after treatment to 
track the developmental trajectory of participants’ motor function. Gross motor outcomes of 
DSM treatment will be compared to published percentile scores of motor function 
development in CP to determine if the trajectory of predicted motor development is altered, 
and to outcomes of intensity-matched conventional treatment. 
 

 
vi  
 
 
 
TABLE 1: SCHEDULE OF STUDY PROCEDURES  
Study Phase 
Screening 
Assessment 
1 (0 week) 
Therapy 
1-18 
Assessment 
2 (6 week) 
Therapy 
19-36 
Assessment 
3 (12 week) 
Therapy 
37-54 
Assessment 
4 (18 week) 
Therapy 
55-72 
Assessment 
5 (24 week) 
Follow 
up (3 
mo) 
Follow 
up (6 
mo) 
Follow 
up (12 
mo) 
Visit Number 
1 
2 
3-20 
21 
22-39 
40 
41-58 
59 
60-77 
78 
79 
80 
81 
Informed 
Consent/Assent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Review 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics/ 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Bayley Scales of 
Infant Development 
X 
X 
 
 
 
 
 
 
 
X 
 
X 
X 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Gross motor function  
(GMFM-66) 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Weight 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Secondary outcomes 
(Postural control, 
physical activity, 
caregiver satisfaction, 
Child Engagement in 
Daily Life) 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Family Empowerment 
Scale 
 
X 
 
 
 
 
 
 
 
X 
 
X 
X 
Rehabilitation (either 
DSM or CONV) 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
Possible video or 
photograph  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

 
page vii 
  
 
 
 
FIGURE 1: STUDY DIAGRAM 
 
 
 
 
.

 
 
 
 
 
 
1 
1 
BACKGROUND INFORMATION AND RATIONALE 
1.1 Introduction 
 
As the most common cause of physical disability in children, CP is a disorder “…of 
the development of movement and posture… attributed to non-progressive disturbances that 
occurred in the developing fetal or infant brain.”1 Given the age at onset and the near-typical 
lifespan,2 those living with cerebral palsy (CP) experience one of the highest number of 
disability-years among all disabling conditions. CP is the most common cause of motor 
disability in children3 with a prevalence that has remained stable over recent decades at 
more than 3 per 1000 births or 10,000 babies per year in the United States despite advances 
in pre- and perinatal care.4,5 An estimated 15 million people currently live with CP 
worldwide. The degree of life participation restriction in those with CP is predicted by the 
degree of motor disability, which varies widely from limitations in balance and coordination 
to full dependence on others for care.6 This relationship between severity of motor disability 
and participation restriction has been reported in infancy,7 childhood,8,9 and adolescence and 
young adulthood.10 Independent of cognitive impairment, the severity of physical disability 
in childhood is a predictor of later romantic relationships11 and independent living in the 
early 30s.12  
The best opportunity to maximize lifelong independence is early in motor 
development when the differences in motor skill between functional levels are relatively 
small and there is the most potential for neuroplastic change. Gross motor function plateaus 
by 4-7 years of age13 after which motor ability is relatively fixed with large skill gaps 
between levels. In fact, the Gross Motor Function Classification System (GMFCS)6 of motor 
severity remains relatively stable throughout childhood and adulthood,14,15 regardless of 
treatment. However, the early years of life are an exception with less stability in GMFCS 
classifications before the age of 2 years.16 There is also growing evidence of a critical period 
of neuroplasticity for motor control centers in the brain. Similar to the development of 
sensory systems, recent work has confirmed that plasticity in the motor system is both 
activity-dependent, and more robust in early as compared to later years.17,18 Moreover, 
maladaptive changes that occur after central nervous injury are difficult to reverse once 
established.19 These observations suggest that there is a window of opportunity for 
interventions applied prior to nearing the developmental peak to improve the trajectory of 
motor development and reduce lifelong physical disability.   
 
How best to optimize motor ability during this narrow window remains unknown. 
Current practice does not reflect key learning principles of typical motor development. 
Typical toddler movement is characterized by a high degree of motor exploration, error and 
movement variability, which are critical factors in the refinement of motor control. Infants 
and toddlers with CP often cannot create these experiences on their own, losing natural 
opportunities to learn more coordinated movements and establish the associated neural 
pathways that control skilled movement. In contrast to their typically-developing peers, 
young children with CP instead repeatedly practice poorly-controlled motor patterns. Our 
work will investigate a promising novel treatment designed to allow infants and toddlers 
with CP to create for themselves motor learning experiences more similar to their typically 
developing peers. This contribution will be significant because the treatment may have the 
potential to improve the trajectory of motor development and reduce lifelong physical 
disability in individuals with CP. The work will increase our understanding of how best to 

 
 
 
 
 
 
2 
optimize the potential of the developing brain to recover after neuromotor injury. As such, 
the proposed work will also inform the early treatment practices for other developmental 
disorders, such as early brain injury, Down Syndrome, and various neurogenetic disorders.  
1.2 Name and Description of Investigational Intervention 
Dynamic Supported Mobility (DSM) - The experimental therapy group will receive 
dynamic weight support (using the ZeroG Gait and Balance training system, Aretech LLC, 
Ashburn, VA) during all therapy time, and the environment will be arranged to encourage 
active motor exploration by the child, in order to promote the motor variability, challenge, 
and error experiences that characterize the typical development of upright motor skills and 
walking. Activities will be graded in difficulty to the child’s ability and will include: moving 
between the floor and standing, walking, squatting to reach the floor, climbing/walking up 
and down steps and inclines, and other typical toddler movements, somewhat similar to a 
play gym for toddlers. The floor area within 3 feet below either side of the overhead track 
for a distance of approximately 20 feet (approximately 120 ft2 total) will be defined with 
colorful thin rubber interlocking mats and arranged with pediatric toys and activities, 
tailored to the child’s interests and to encourage motor skills just beyond his/her current 
ability level. The dynamic support system continuously provides a constant amount of 
weight assistance (as determined by the therapist) by controlling the length of the cable 
joining the harness and track and by moving along the overhead track as the user moves 
about the space (i.e. cable lengthens if child moves to the floor and shortens if child climbs 
up steps, with no lag time). The user’s movements are not restricted at all within this space. 
This arrangement works well to keep children within the limits of the overhead track and 
provide ample opportunity and space for motor play and exploration. Initial amount of 
weight assistance will be determined during the first therapy session by the level that allows 
walking and squatting to reach the floor with the least amount of assistance from the 
therapist. Weight assistance will be gradually reduced during the treatment phase as postural 
control and coordination improve.  The therapist will minimally assist the child as needed to 
perform the movements he/she initiates. 
 
1.3 Relevant Literature and Data 
  
The proposed intervention has been systematically developed and pilot-tested 
consistent with a stage model for behavioral therapies.20 The treatment was designed to 
incorporate overlapping principles of neurorehabilitation and infant motor learning in a 
context that promotes upright mobility skill and postural control development. 
Treatment development.   
  
Principles of neurorehabilitation. Despite increasing evidence of early critical 
periods for neuroplasticity,17,18 there remains little application to individuals with CP. 
Treatments addressing secondary musculoskeletal impairments such as muscle and bone 
abnormalities that develop in response to poor motor control remain the most common 
treatment approaches.21 These interventions are important to manage the course of CP, but 
do not address the primary impairment of poor neural control of movement.1 The most 
effective rehabilitation programs include intensive, early, and challenging motor practice,22-

 
 
 
 
 
 
3 
24 and these principles are supported by training-dependent plasticity in cortical structures.25-
27 Variability in movement patterns during rehabilitation further enhances motor 
outcomes28,29 and reflects complex motor skill.30 Salience is the meaningfulness of the 
training to the patient which promotes active engagement and facilitates neuroplasticity.31,32 
Finally, the critical role of error in motor learning and rehabilitation has been increasingly 
recognized,33,34 with diminished long-term gains when error is eliminated from practice.35  
 
Principles of infant motor learning. It is perhaps no coincidence that many 
neurorehabilitation principles for training motor coordination are also important components 
of typical infant motor learning. Motor exploration is the basis for all infant motor 
development36 and in fact, practice is a more important developmental factor than age in 
helping infants learn to overcome their weak muscles and poor balance.37 Typical 12- to 19-
month-old children fall an average of 17 times per hour of free play,38 and falling (motor 
error) is believed to play an important a role in learning to walk.39 Adolph has emphasized 
the role of inherent variability in motor development,40 and more stereotyped and 
predictable motor patterns (i.e. less capacity for variability and adaptability) are observed in 
healthy infants when free movement is restricted.41 Finally, the degree of salience in a visual 
cue can determine whether an infant will move to it.42 Adhering to these key principles of 
infant motor learning allows the training program to closely reflect the motor exploration 
experiences that characterize the beginning stages of walking skill, experiences that without 
support, infants and toddlers with CP are not able to create on their own. We call the 
intervention dynamic supported mobility (DSM) and additional details of its development 
are included in the published manuscript.43 
Feasibility testing.  
We conducted a single-subject research design pilot study to evaluate the safety, 
feasibility, and tolerability of the intervention, as well as the appropriateness of the primary 
outcome measure, in the target population.43 Five children (aged 12-27 months, GMFCS I-
III) participated in the study with repeated measures of gross motor function (GMFM-66) 
during 6-week baseline and treatment phases, and after a 6-week follow-up phase. No 
adverse events occurred. Attendance rate was 81% for Participant 3 and 100% for all others. 
All therapy sessions were videotaped for later activity coding to validate the motor 
outcomes.  
Table 1 presents rates of motor development in each study phase, calculated using 
the split middle technique for single-subject study data,44 and relative rates of motor 
development for the treatment (Treatment/Baseline) and follow-up phases (Follow-
up/Baseline) compared to baseline. Values greater than 1.0 for relative rates of change 
represent increased rate of motor development, and values less than 1.0 represent decreased 
rate of motor development compared to the baseline rate. Participants 1-4 demonstrated rates 
of motor development during treatment that were 3.8 to 15.1 times greater than their 
respective baseline rates. All participants maintained their treatment gains, but returned to 
slower rates of motor development during follow-up. Participant 3 began walking alone with 
the dynamic support during the first therapy session. She did not start walking on her own at 
home, until approximately three weeks later, suggesting that the treatment allowed her to 
practice more advanced skills than she was able to do on her own. Participant 5 
demonstrated improvement during treatment, but the rate of development was less than her 
baseline rate (0.3). This child made large gains during baseline when she started walking on 

 
 
 
 
 
 
4 
her own (at 16 months of age), and as a result there is no indication from these data that the 
intervention improved her motor ability beyond what could be predicted. She was the least 
affected participant (above the 50th percentile of GMFCS level I) and likely not an ideal 
candidate, which informed the refinement of participant selection criteria. Participant 4 was 
the most impaired child and demonstrated the largest relative rate of change.  
 
Table 1. Motor development rates, representing average GMFM change per week. Relative rates of 
change compare treatment and follow-up phases to baseline (with 1.0 representing equal rates of 
change). 
  
 
Figure 2 presents the raw data and net change scores (treatment change minus 
baseline change). The net treatment change for Participant 5 was -5.7 as a result of her large 
improvement during baseline. Net change scores for Participants 1-4 ranged from 2.4-9.7, 
each exceeding the minimal clinically important difference values for treatments that have a 
large effect size (1.5 for GMFCS level II and 1.3 for GMFCS level III).45 In summary, the 
treatment and training schedule were feasible with changes sustained at short-term follow-
up, and continued systematic investigation is warranted. 
 
Figure 2. Motor function outcomes. Net change scores for each participant are included 
in the legend. 
 
 
Motor Development Rates 
Relative Rates of Change 
ID 
Baseline 
Treatment 
Follow-up 
Treatment/ Baseline 
Follow-up/ Baseline 
1 
0.05 
0.55 
0.04 
10.8 
0.7 
2 
0.16 
0.61 
0.08 
3.8 
0.5 
3 
0.30 
2.05 
0.20 
7.0 
0.7 
4 
0.05 
0.77 
0.24 
15.1 
4.6 
5 
1.56 
0.46 
-0.06 
0.3 
-0.04 

 
 
 
 
 
 
5 
Treatments that improve a child’s motor function by one GMFCS level would 
achieve a large and impactful change that exceeds the level of improvement realized by 
currently available treatments for individuals with CP.14,15,46 Our preliminary work included 
just six weeks of DSM treatment. Six weeks of treatment was sufficient for one child 
(Participant 3) to be reclassified from a level II to I. For the other three participants 
who would meet the proposed selection criteria (Participants 1, 2, and 4), if improvement 
had continued at the observed rate, approximately 12 weeks of treatment would have been 
adequate for them to have improved one functional level. However, it cannot be assumed 
that the rate of improvement will be constant with longer treatment durations. For this 
reason, outcomes after 12, 18 and 24 weeks of treatment will be evaluated to establish a 
more complete understanding of the treatment duration-response relationship and the full 
potential of the treatment to alter the trajectory of motor development. These data support 
the feasibility of Aim 1 and provide the foundation for Hypothesis 1.1 that at least 12 weeks 
of DSM treatment will effectively alter the trajectory of motor development to a degree that 
is sustained at longer term follow-up.  
For the four children who would meet the proposed selection criteria, all training 
videos were coded to investigate if changes were indeed related to the treatment provided. 
Amounts of training time spent doing activities related to each relevant GMFM subscale (C. 
Crawling & Kneeling, D. Standing, and E. Walking, Running & Jumping) were correlated to 
net changes in the respective subscale. A high degree of variance in subscale outcomes was 
explained by the amount of training time (r2 = 0.80, 0.74, 0.98, 1.00, respectively). Video 
coding also revealed a high level of motor engagement and falls, as intended. The 
relationship between number of falls and total GMFM-66 change was quite strong (r=0.80), 
suggesting that falling and learning may have happened simultaneously. Table 2 presents 
video coding results (note: raw scores for activity subscales are not shown). These video 
coding data provide the foundation for Hypothesis 1.2 that the amounts of motor error, 
variability and engagement incorporated into the DSM treatment will be related to outcome.  
 
Table 2. Video coding results, including variance explained (r2) between training time in each GMFM activity 
subscale (C, D, and E) and motor change, motor engagement, and average number of falls per session. 
 
C. Crawling & 
Kneeling 
D. Standing 
E. Walking, Running 
& Jumping 
 
ID 
NET 
change 
Minutes/ 
session 
NET 
change 
Minutes/ 
session 
NET   
change 
Minutes/  
session 
r2 
Motor 
engagement 
Falls 
1 
7.1 
11:56 
10.3 
10:58 
1.4 
03:32 
0.80 
91% 
11 
2 
2.4 
09:08 
17.9 
12:46 
0.0 
03:16 
0.74 
87% 
6 
3 
11.9 
06:57 
48.7 
10:43 
29.2 
09:13 
0.98 
95% 
17 
4 
11.9 
11:23 
10.3 
09:42 
5.6 
05:01 
1.00 
88% 
14 
 
 
The proposed study involves no more than minimal risk research and no adverse 
events occurred in preliminary work. These circumstances support the foundation of 
Hypothesis 2.1 that DSM treatment will pose no more risk to participants than current 
rehabilitation practice.  

 
 
 
 
 
 
6 
Two methods of interpreting the preliminary data support prospective comparison of 
the functional outcomes of DSM treatment to conventional rehabilitation practice. First, the 
four participants who would meet the proposed selection criteria were receiving other 
rehabilitation services throughout the study and demonstrated rates of motor development 
during the DSM treatment phase that were 3.8 to 15.1 times their respective rates of motor 
development during the baseline phase (Table 1). This suggests that the DSM treatment 
significantly accelerated their individual rates of motor skill attainment with conventional 
rehabilitation services. However, motor development is not always linear,47 so this approach 
is not sufficient to determine the treatment’s futility compared to other treatments. Second, 
the same four participants all demonstrated net changes (ranging from 2.4-9.7, Figure 2) 
after only six weeks of treatment that exceeded the corresponding minimal clinically 
important difference values for treatments that have a large effect size (1.5 for GMFCS level 
II and 1.3 for level III).45 However, caution should be taken as these minimal clinically 
important difference values were determined from a sample of children aged 4-18 years, and 
while unknown, it is possible that the minimal clinically important difference values would 
be larger earlier in development. Although promising, prospective comparison to intensity-
matched current rehabilitation intervention is needed to confirm the potential advantages of 
DSM treatment prior to progression to a larger efficacy trial. These data support the 
foundation of Hypothesis 2.2 that children who receive DSM treatment will demonstrate 
greater gains in gross motor function than participants who receive equal amounts of CONV 
treatment.  
 
Other Relevant Literature 
 
Determining the optimal dose of pediatric rehabilitation services for children with 
CP and other developmental disabilities has been identified as a national priority.48  Yet, the 
majority of research in the field has not explored dose-response outcomes for various 
interventions. The convenient, rather than scientifically-grounded, dosing of neuromotor 
rehabilitation historically offered during clinical trials often limits the validity and 
comprehensiveness of the research findings. Investigation of treatment response over a 
duration long enough to reach an anticipated behavioral plateau in the early stages of 
scientific inquiry more adequately prepares an experimental rehabilitation treatment for 
Phase III efficacy evaluation.49  
Both 
the 
National 
Institute 
of 
Neurological 
Disorders 
and 
Stroke 
(www.ninds.nih.gov) and leaders in neurology50 and neurorehabilitation51 suggest that early 
clinical trials are the appropriate stage at which to evaluate the futility of a new treatment 
compared to another treatment or standard of care. These data are critical in determining if 
and how the science should progress in a definitive Phase III trial. Dobkin further 
emphasizes that while “a nonactive placebo may be the only therapy in a drug trial if no 
standard drug therapy exists, comparing a specific rehabilitation treatment to nothing is no 
longer acceptable.” (2009) The intensity of treatment (minutes per week) in the proposed 
study will approximate the average amount of physical therapy received by young children 
with CP in the United States. The average amount of physical therapy is 82 (SD 60) minutes 
per week in the United States, and 90 (SD 60) minutes per week in the Philadelphia 
metropolitan area.52 The 90 minutes per week of either treatment in the proposed study 
reflects this current intervention practice. However, the wide variability in the standard 

 
 
 
 
 
 
7 
amount of services means that not all children would receive this intensity outside of the 
research study. This variability in current practice is a common issue in identifying 
“standard of care” in rehabilitation trials. However, it has been determined in gold-standard 
trials that matching the treatment intensity of the experimental group is the most important 
component of the “control” group,24,53 and our approach reflects this standard. 
 
1.4 Compliance Statement 
 
This study will be conducted in full accordance all applicable Children’s Hospital 
of Philadelphia Research Policies and Procedures, all applicable Federal and state laws and 
regulations, and the Good Clinical Practice: Consolidated Guideline approved by the 
International Conference on Harmonisation (ICH). All episodes of noncompliance will be 
documented. The investigators will perform the study in accordance with this protocol, will 
obtain consent and assent, and will report unanticipated problems involving risks to subjects 
or others in accordance with The Children’s Hospital of Philadelphia IRB Policies and 
Procedures and all federal requirements. Collection, recording, and reporting of data will be 
accurate and will ensure the privacy, health, and welfare of research subjects during and 
after the study.  
 
2 
STUDY OBJECTIVES 
2.1 Primary Objectives (or Aims) 
Aim 1. To determine the optimal treatment duration of dynamic supported mobility (DSM) 
treatment in infants and toddlers with cerebral palsy, between 6 to 24 weeks of treatment. 
Hypothesis 1.1. Gross motor ability (measured by the GMFM-66) will exceed 
individual predicted values in infants and toddlers with cerebral palsy after 12, 18, 
and 24 weeks of DSM treatment, and gains will be maintained at 3, 6 and 12 month 
follow-up points.  
Hypothesis 1.2. Gross motor function gains will be positively related to the amount 
of motor error, variability and engagement experienced during DSM treatment.  
Aim 2. To determine the futility of dynamic supported mobility compared to conventional 
rehabilitation in infants and toddlers with cerebral palsy. 
Hypothesis 2.1. The frequency of adverse events among participants who receive 
DSM treatment and those who receive conventional (CONV) treatment will not 
differ by greater than 10 percent.  
Hypothesis 2.2. Participants who receive DSM treatment will demonstrate 
significantly greater improvements in gross motor ability (measured by the GMFM-
66) than participants who receive equal amounts of CONV treatment, and these 
differences will be maintained at each follow-up point.  

 
 
 
 
 
 
8 
2.2 Secondary Objective (or Aim) 
The secondary objective is to: 
• Compare physical activity at home, postural control, engagement in daily life, caregiver 
satisfaction and cognition in the dynamic supported mobility (DSM) therapy group to 
the conventional (CONV) therapy group. 
 
3 
INVESTIGATIONAL PLAN 
3.1 General Schema of Study Design 
The proposed study is a single-blind, randomized exploratory clinical trial with 
repeated assessments during a 24-week treatment phase and at three follow-up points over 
12 months after treatment to track the developmental trajectory of participants’ motor 
function. Gross motor ability will be compared to published percentile scores of motor 
function development in CP to determine if the trajectory of predicted motor development is 
altered, and to outcomes of intensity-matched conventional treatment to determine if 
continued Phase III investigation is warranted. 
3.1.1 Screening Phase 
Candidate screening will be conducted by the primary research therapist using the 
protocol inclusion and exclusion criteria. The parent or legal guardian must provide written 
informed consent prior to the start of any study activities. Written assents of minors will not 
be obtained due to the age of the participants.  
3.1.2 Study Treatment Phase (start of the study intervention) 
Children will be able to continue their outside therapies, if their families’ choose to 
do so. Whether they reduce or continue their pre-enrollment therapy schedule, families will 
be asked to maintain the schedule of outside physical therapy constant throughout the 
treatment phase. It is anticipated that most children will be receiving early intervention 
therapy services in the home. Other medical care will be documented but not restricted. If 
parents sign CHOP’s standard HIPAA authorization, we will request copies of outside 
therapy notes to assist with documentation of co-occurring treatments. Treatment will start 
within one week of Assessment 1 and will be delivered by the primary or secondary research 
physical therapist, both of whom will be trained using the study manual to provide each type 
of treatment. We will follow intent to treat procedures such that no child will be withdrawn 
from the study for failing to adhere to the therapy schedule. A training log will be 
maintained for each session. One session per week will be videotaped (if separate consent is 
provided) for quality control to ensure that activities between the treatments remain different 
and are consistent with the distinguishing characteristics.  
After enrollment and the initial assessment, participants will be randomized to 
receive either DSM or conventional (CONV) treatment, using a randomization scheme to 
ensure that motor ability does not differ at baseline. Participants will also be randomly 
assigned to either the primary or secondary research therapist who will each provide both 

 
 
 
 
 
 
9 
types of treatments, to minimize any differences related to individual therapist. Treatment in 
both groups will occur at an intensity of 3 times per week for 30 minutes.  
DSM treatment. Children will receive dynamic weight support (ZeroG®, Aretech 
LLC, Ashburn, VA) during all DSM treatment time. The environment will be arranged to 
encourage active motor exploration, somewhat similar to a play gym for toddlers, to 
promote the motor variability, engagement, and error experiences that characterize the 
typical development of upright motor skills and walking. The floor area within 3 feet below 
either side of the overhead track for a distance of 20 feet (approximately 120 ft2 total) will 
be defined with colorful thin rubber interlocking mats and arranged with pediatric toys and 
activities, tailored to the child’s interests and to encourage motor skills just beyond his/her 
current ability. This arrangement worked well in pilot work to keep children within the 
limits of the overhead track and provide ample opportunity and space for motor play and 
exploration. Initial amount of weight assistance will be determined by the level that allows 
walking and squatting to reach the floor with the least amount of assistance from the 
therapist, up to a maximum of 40% of the child’s weight. Greater than 40% weight support 
produces significant alterations in normal walking biomechanics in healthy adults 
(unpublished data, communication with system inventor, J. Hidler, PhD). Amount of weight 
assistance will be re-assessed at the start of each session, and will be gradually reduced as 
postural control and coordination improve to the minimum amount that allows walking and 
squatting to reach the floor with the least amount of assistance from the therapist. The 
therapist will minimally assist the child as needed to perform the movements he/she 
initiates.  
CONV treatment. The conventional treatment group will receive traditional, 
therapist-directed pediatric physical therapy. Therapy will focus on early gait training 
strategies and encouragement of “normal” movement patterns for walking and other age-
appropriate movements, with manual guidance or correction of atypical movements from the 
therapist. This group may use assistive devices, orthoses, and may receive static body 
weight support for gait training. Therapy activities will be performed in blocks of practice, 
with the specific activities and level of therapist assistance tailored to each child. Examples 
include: using a posterior rolling walker with ankle foot orthoses (braces), physically guided 
practice of standing from the floor through half kneeling, manual correction of side steps 
while cruising at a bench, and repeated sit to stand practice from a small chair. The 
distinguishing characteristics of each treatment are listed in Table 4. 
3.1.3 Follow-up Phase 
The treatment phase will end after 24 weeks of treatment. Three follow-up 
assessments will occur at 3, 6 and 12 months after treatment ends.  
3.2 Allocation to Treatment Groups and Blinding 
After the initial GMFM-66 score from Assessment 1 is obtained, participants will be 
randomized to either the CONV or DSM treatment, using a randomization scheme to stratify 
by baseline motor ability. This will ensure that the groups do not differ in motor ability at 
baseline. Participants will also be randomly assigned to either the primary or secondary 
research therapist who will each provide both types of treatments, to minimize any 
differences related to individual therapist. A blinded assessor will collect all outcomes 

 
 
 
 
 
 
10 
measures. Blinding of participants to treatment group is not feasible with the proposed 
interventions.  
3.3 Study Duration, Enrollment and Number of Sites 
3.3.1 Duration of Study Participation 
Total study duration is 18 months, including 6 months of a treatment phase and 12 
months of a follow-up phase. 
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected 
All testing procedures and interventions will occur in the Center for Rehabilitation at 
CHOP. Sixty participants with CP between the ages of 1-3 years will be recruited for the 
study. It is expected that enrollment of 60 participants will produce 42 evaluable datasets.  
3.4 Study Population 
3.4.1 Inclusion Criteria 
1) 12-36 months of age  
2) Gross motor function below the 10th percentile for age (Bayley Scales of Infant and 
Toddler Development, BSID-III, corrected for gestational age, if applicable, under the 
age of two years). 
3) Diagnosis of CP or neurological sign associated with CP (i.e. spasticity).  
4) Ability to initiate pulling to stand at a surface (Score of 1 on GMFM Item 52).  
5) Cognitive ability to follow one-step commands.  
3.4.2 Exclusion Criteria 
1) Secondary orthopedic, neuromuscular or cardiovascular condition unrelated to CP. 
2) General muscle hypotonia, without other neurological signs associated with CP.  
3) Independent walking ability (Score of 3 on GMFM Item 69 – Walks forward 10 steps).  
4) At or above the 50th percentile of GMFCS Level I. 
5) History of surgery or injury to the lower extremities in the past 6 months. 
Subjects that do not meet all of the enrollment criteria may not be enrolled. Any violations 
of these criteria must be reported in accordance with IRB Policies and Procedures.  
 
4 
STUDY PROCEDURES 
Please refer to table 1 “Schedule of study procedures” 

 
 
 
 
 
 
11 
4.1 Screening Visit 
• Informed Consent 
• Physical Therapy Examination 
• Medical Record Review 
• BSID-III, gross motor scale 
• Review of Inclusion and Exclusion criteria 
4.2 Treatment Phase 
4.2.1 Assessment sessions 1-5 
• Randomization (Assessment 1 only) 
• Weight 
• Gross motor function (GMFM-66) 
• Secondary outcomes (Postural control, physical activity, caregiver satisfaction, Child 
Engagement in Daily Life) 
• BSID-III, cognitive scale (Assessments 1 and 5) 
• Family Empowerment Scale (Assessments 1 and 5) 
• Possible video or photograph 
4.2.2 Treatment sessions 1-72 
• Rehabilitation (three 30-minute sessions per week of either DSM or CONV 
treatment)  
• Possible video or photograph 
4.3 Follow-up Phase 
4.3.1 Follow-up assessments (3, 6 and 12 months) 
• Gross motor function (GMFM-66) 
• Secondary outcomes (Postural control, physical activity, caregiver satisfaction, Child 
Engagement in Daily Life) 
• BSID-III, cognitive scale (6 and 12 month follow-ups) 
• Family Empowerment Scale (6 and 12 month follow-ups) 

 
 
 
 
 
 
12 
• Possible video or photograph 
4.4 Subject Completion/Withdrawal 
Subjects may withdraw from the study at any time without prejudice to their care.  
Intent to treat procedures will be followed such that participants will not be withdrawn from 
the study by the investigators for lack of adherence to the treatment schedule. Participants 
will not be withdrawn from the study for missing treatment sessions. The Investigator or the 
Sponsor (if applicable) may also withdraw subjects who violate the study plan, or to protect 
the subject for reasons of safety or for administrative reasons. It will be documented whether 
or not each subject completes the clinical study. If the Investigator becomes aware of any 
serious, related adverse events after the subject completes or withdraws from the study, they 
will be recorded in the source documents and on the CRF. 
4.4.1 Early Termination Study Visit 
Subjects who withdraw from the study will have all procedures enumerated for 
Assessment 5 completed as the early termination visit.  
4.4.2 Make-up treatment sessions 
If subjects miss greater than 20% of therapy sessions, they will be given the option to 
make up treatment sessions at the end of the study, after Assessment 5 (at 24 weeks). If six 
or more make-up sessions are completed, a final post-treatment visit will be completed, 
which will include a repeat of all procedures enumerated for Assessment 5. 
 
5 
STUDY EVALUATIONS AND MEASUREMENTS 
5.1 Screening and Monitoring Evaluations and Measurements 
In addition to the measures listed below, the study database and data collection 
instruments will also include relevant data elements from the NINDS Common Data 
Elements (CDE), including elements on Demographics, Health History, Physical Exam, 
Treatment/Intervention 
Data, 
Protocol 
Experience, 
and 
Safety 
Data 
(http://www.commondataelements.ninds.nih.gov/General.aspx#tab=Data_Standards). 
5.1.1 Medical Record Review 
The CHOP medical record will be accessed and reviewed for potential candidates 
who are patients, as part of the recruitment and screening process. Non – CHOP patients will 
be asked to provide their relevant medical records with written HIPPA authorization from 
their medical facility. Screening for eligibility based on medical record review will include: 
date of birth and review of any significant history of orthopedic, neurologic or cardio-
pulmonary conditions.  
5.1.2 Physical Examination 
• Physical therapy examination 

 
 
 
 
 
 
13 
• Ability to initiate pulling to stand, score of at least 1 on GMFM Item 52 (inclusion 
criterion).  
• BSID-III, gross motor scale (inclusion criterion)  
5.2 Efficacy Evaluations 
5.2.1 Gross Motor Function Measure (GMFM) 
The primary outcome is the GMFM-66, a Rasch-analyzed measure of gross motor 
function designed for children with CP.54 Computation of the GMFM-66 score involves 
statistical weighting of the raw item scores for difficulty. This score will also be used with 
the patient’s age to determine GMFCS percentile rank.55 
5.2.2 Secondary Outcomes  
Postural control. Using computerized posturography, participants will sit for 3-5 ten 
second trials on the force platform while center of pressure data are collected. This process 
will be repeated in kneeling and standing positions if the participant is able to maintain these 
positions. Center of pressure data will be interpreted using nonlinear measures of analysis. 
We will also administer the Early Clinical Assessment of Balance test, which is a test 
designed to measure postural control in young children with physical disabilities.  
Physical activity. A wireless activity monitor will be provided to the caregiver, who 
will be instructed on use of the monitor at home, with a goal of recording 5 total hours of the 
child’s free play in the following week. An envelope will be provided to return the activity 
monitor. Amount and magnitude of physical activity will be calculated using corresponding 
software. 
Caregiver satisfaction. One caregiver of each participant will rate their child’s 
performance on the caregiver’s self-identified goals, and the their own (caregiver’s) 
satisfaction with the child’s performance using the Canadian Occupational Performance 
Measure.  
Child Engagement in Daily Life. One caregiver of each participant will complete the 
Child Engagement in Daily Life Measure to obtain a measure of the child’s participation in 
play in daily life. 
5.2.3 Weight 
The child’s weight will be measured at each assessment to ensure that the percent 
weight support during treatment sessions is accurate.  
5.2.4 Bayley Scales of Infant and Toddler Development, cognitive scale  
The cognition age equivalent obtained from the BSID-III will be used as a covariate 
as patient cognition is known to influence response to rehabilitation.56,57 To avoid a learning 
effect from repeated testing, this will be completed only every 6 months.  
5.2.5 Family Empowerment Scale  
One caregiver of each participant will complete the Family Empowerment Scale to 
obtain a measure of the caregiver’s self-efficacy, also known to influence response to 

 
 
 
 
 
 
14 
rehabilitation.58 To avoid caregivers remembering their prior responses, this will be 
completed only every 6 months.  
5.2.6 Possible video or photograph  
One treatment session will be videotaped each week to quantify participant error 
experience (number of falls), motor variability (time spent in one motor activity before 
moving to the next), and salience or motor engagement (time engaged in a dynamic motor 
activity) during DSM treatment, allowing evaluation of the relationship of these factors to 
treatment response. The videotaped sessions will also be coded for the amount of time 
participants spend doing activities in each of the GMFM subscales, to allow evaluation of 
the relationship between time spent in each activity category and outcome in each subscale. 
Randomly selected videos will also be used for quality checks to ensure that the two 
treatments remain different and consistent with the distinguishing characteristics of each 
group.  
Occasional photographs may be taken, if separate consent is provided, for educational 
or scientific purposes, or as souvenirs for the children.  
5.3 Safety Evaluation 
Subject safety will be monitored by adverse events. Anticipated and unanticipated 
adverse events will be recorded to confirm that DSM treatment does not pose greater risks 
than current interventions.  
 
6 
STATISTICAL CONSIDERATIONS 
6.1 Primary Endpoint 
The primary endpoint will be the change in GMFM (Gross Motor Function Measure) 
from baseline to each post-treatment assessment session. 
 
6.2 Statistical Methods 
6.2.1 Baseline Data  
Baseline characteristics for the total sample and by treatment group will be 
summarized by standard descriptive summaries (including mean, standard deviation, 
median, minimum, maximum and range for continuous variables and frequency counts and 
percentages categorical variables). We will also report the 95% confidence interval for 
pertinence means and proportions. Baseline characteristics in each group will be compared 
using two-sample tests, including t-tests, the Mann-Whitney test, and chi-square tests, as 
appropriate for the respective type of data.  
6.2.2 Efficacy Analysis 
For the analysis of Aim 1, Hypothesis 1.1 (Gross motor ability will exceed predicted 
values after DSM treatment and gains will be maintained at follow-up), GMFCS percentile 
ranks will be obtained after 6, 12, 18 and 24 weeks of treatment based on actual GMFM-66 

 
 
 
 
 
 
15 
scores and age, and will be compared to predicted percentile ranks based on age and initial 
GMFM-66 score. Mean values and 95% confidence intervals will be calculated for actual 
and predicted scores. Optimal treatment duration will be identified as the maximum change 
observed at the related time point which is maintained during the following period. If 
maximum change occurs after 24 weeks, this time will be considered the optimal duration. 
Spearman correlation will be utilized to analyze Hypothesis 1.2 (Outcomes will be related to 
the amount of error, variability and engagement during treatment), to estimate the 
relationship between motor improvement and the amount of motor error, variability and 
engagement experienced during treatment.  
To address Aim 2, Hypothesis 2.2 (Participants who receive DSM treatment will 
demonstrate greater improvements than participants who receive CONV treatment, and the 
differences will be maintained at follow-up) will be analyzed by comparing GMFM-66 
outcomes between participants receiving DSM treatment and those receiving CONV 
treatment. Baseline characteristics in each group will be compared using two-sample tests, 
including t-tests, the Mann-Whitney test, and chi-square tests, as appropriate for the 
respective type of data. We will then use a univariate approach for comparing the two 
treatments using analyses of variance and covariance (ANCOVA). Measurements at 6, 12, 
18 and 24 weeks, as well as at both follow-up points after treatment will be individually 
compared between the two treatment conditions using baseline score, cognition and 
caregiver self-efficacy as covariates. We will also use a multivariate approach using linear 
mixed effects model59 or the Generalized Estimating Equation (GEE).60 The advantage of 
using the mixed effects model or the GEE approach is that they will not drop subjects from 
the analysis due to not having measurement at any of the post-treatment time points. Also, 
such analyses will allow us to examine the between subjects effects which represent a factor 
with two levels (treatment conditions) and within subjects effects which represent time 
effects (pre and post measurements) and a time by condition interaction. The random effect 
model will be implemented utilizing SAS Proc Mixed and the GEE will be implemented by 
SAS Proc Genmod. (SAS/STAT User's Guide, 2004, Version 9. Cary, NC: SAS Institute, 
Inc). Cognition and caregiver self-efficacy will be included as covariates in these analyses. 
Two-sided p values of less than 0.05 will be considered statistically significant. Similar 
procedures will be used for the analysis of secondary outcomes, with appropriate tests for 
parametric (postural control, physical activity) and non-parametric measures (caregiver 
satisfaction, Child Engagement in Daily Life). 
6.2.3 Safety Analysis 
To address Hypothesis 2.1 (Adverse events will not differ by greater than 10% 
between treatments), type and frequencies of adverse events will be presented descriptively 
by treatment. A magnitude of difference of less than 10% will be considered as similar 
between treatments. 
6.3 Sample Size and Power 
This is a proof of concept futility study and to keep the number of participants to the 
minimum necessary, sample size estimation was not driven to achieve a specific effect size 
or statistical power, but rather to derive estimates and confidence intervals. A minimum of 
15 subjects receiving a novel treatment has been recommended for early studies of dose-
response and futility in neurorehabilitation.51 We also calculated predicted change and 95% 

 
 
 
 
 
 
16 
confidence intervals for both treatments. Predicted change after DSM treatment was 
determined from the data of the four pilot children who would meet the proposed selection 
criteria. A mean GMFM-66 increase of 5.3 was observed after six weeks of treatment. 
Assuming such change will be doubled after 12 or more weeks of treatment, a 10.6 increase 
from baseline is predicted as a minimum change after DSM treatment. Predicted change 
after CONV treatment was determined from maximum change in published GMFM-66 
scores over six months in a 24 month old child classified as GMFCS level II.55 A 1.8 
increase from baseline is predicted after CONV treatment. We estimated that with a sample 
size of 17 participants receiving each treatment, a 2-sided 95% confidence interval for the 
difference in GMFM-66 will extend +/- 6 from the observed difference assuming that the 
common standard deviation (SD) is 9 (nQuery Advisor 6.0), which was larger than observed 
in the pilot data for a conservative estimate. An additional 8 children (4 in each group) will 
be enrolled to account for an anticipated attrition rate of 20%. Based on random assignment, 
21 participants will receive DSM treatment, and another 21 will receive CONV treatment. 
 
7 
SAFETY MANAGEMENT 
7.1 Clinical Adverse Events 
Clinical adverse events (AEs) will be monitored throughout the study.  
7.2 Adverse Event Reporting 
Since the study procedures are not greater than minimal risk, SAEs are not expected. 
If any unanticipated problems related to the research involving risks to subjects or others 
happen during the course of this study (including SAEs) they will be reported to the IRB in 
accordance with CHOP IRB SOP 408: Unanticipated Problems Involving Risks to Subjects. 
AEs that are not serious but that are notable and could involve risks to subjects will be 
summarized in narrative or other format and submitted to the IRB at the time of continuing 
review. 
  
8 
STUDY ADMINISTRATION 
8.1 Treatment Assignment Methods 
8.1.1 Randomization 
After the initial GMFM-66 score from Assessment 1 is obtained, participants will be 
randomized to either the CONV or DSM treatment, using a randomization scheme to stratify 
by baseline motor ability. This will ensure that the groups do not differ in motor ability at 
baseline. Participants will also be randomly assigned to either the primary or secondary 
research therapist who will each provide both types of treatments, to minimize any 
differences related to individual therapist. A blinded assessor will collect all outcomes 
measures. Blinding of participants to treatment group is not feasible with the proposed 
interventions.  

 
 
 
 
 
 
17 
8.1.2 Blinding 
A blinded assessor will collect all outcomes measures. Blinding of participants to 
treatment group is not feasible with the proposed interventions.  
8.2 Data Collection and Management 
Hard copies of case report forms and source data will be stored in a locked cabinet in a 
locked office. Electronic source data will be stored on a network share drive with access 
controlled by the PI. All data will be entered and stored in a project-specific REDCap 
(Research Electronic Data Capture) database. The database will be password-protected and 
daily backups will be stored. It will incorporate range checks and between-variables 
consistency checks to ensure quality control. 
The electronic postural control data will be shared with researchers (Nicholas 
Stergiou, PhD and his team) at University of Nebraska Omaha, who are experts in nonlinear 
analysis of biomechanical data and will assist our team in interpreting these data. A portion 
of the treatment videos will be shared with motor development experts (Karen Adolph, PhD 
and her team) at New York University (NYU) who will assist our team in coding the videos 
for structure of walking behavior using their established methods of detailed infant 
movement analysis. The data files will stored in a secure, password protected electronic 
location, and will be regularly backed up.  
8.3 Confidentiality 
All data and records generated during this study will be kept confidential in 
accordance with Institutional policies and HIPAA on subject privacy and that the 
Investigator and other site personnel will not use such data and records for any purpose other 
than conducting the study. Participants will be assigned a unique identifier that contains no 
protected health information. Access to all data will be controlled by the PI.  No identifiable 
data will be used for future study without first obtaining IRB approval. The investigator will 
obtain a data use agreement between the provider (the PI) of the data and any recipient 
researchers (including others at CHOP) before sharing either limited or identifiable datasets.  
8.4 Regulatory and Ethical Considerations 
8.4.1 Data and Safety Monitoring Plan 
The incidence of adverse events is expected to be low in this single-site minimal risk 
research. The PI will be responsible for monitoring the data and safety of all participants. All 
study procedures will receive IRB approval prior to recruitment or enrollment of 
participants. In addition to the data management procedures outlined above, the PI will hold 
biweekly study team meetings to evaluate the safety and progress of all research procedures. 
Standard procedures for all data collection methods will be reviewed at the start and 
periodically throughout the study. Data checks for errors will be performed prior to analysis. 
Training log review and random video checks will be conducted regularly to ensure that the 
rehabilitation programs are delivered as intended. The PI will be actively involved in 
reviewing the progress of each study participant and will bring to the attention of the IRB 
adverse events and unexpected problems. Unexpected safety concerns will also be 
communicated with the NINDS Program Official in accordance with study regulations. 

 
 
 
 
 
 
18 
Additionally, if we experience adverse events in more than 15% of total participants, we will 
appoint a Study Monitoring Committee to review the safety events that occurred and 
monitor safety for the remaining duration of the study. 
8.4.2 Risk Assessment 
All treatment and assessment activities in the proposed research present no more 
than minimal risk to study participants. Children will have one-on-one supervision at all 
times during the assessment and treatment procedures by a licensed pediatric physical 
therapist. Risks include those involved with any pediatric physical therapy session or toddler 
play session, including bumps and bruises from falling or crashing into toys, and the 
unlikely possibility of muscle strain or soreness from overuse. The environment will be 
prepared such that only items safe for toddlers and young children will be in the treatment 
and assessment areas.  
DSM treatment, which encourages falling, will occur over a floor of thin rubber mats 
to minimize the impact of falls. The weight support harness for DSM therapy is custom-
made for the target age range, includes special provisions for small bodies and sensitive 
skin, such as narrow straps and use of neoprene, and will also prevent the impact of falls. 
The harness may prevent or reduce the impact of falling. Parents will be advised to dress the 
children in slim-fitting garments that have sleeves and their axilla areas will be checked 
periodically to assure that there is no skin redness from the harness. If children experience 
any discomfort with the harness, it will be repositioned until it is comfortable.  
 
Additionally, protected health information will be collected as part of study records, 
and breaches of this information outside of the study team resulting in loss of confidentially 
is an unlikely but potential risk. We will follow CHOP policies to ensure compliance with 
HIPAA and IRB regulations for safeguarding participant information to protect against loss 
of confidentiality. Electronic data will be stored in secure, HIPAA-compliant, password-
protected systems. Hard copies of data collection instruments and training logs will be 
stored in a locked cabinet in the PI’s locked office. Participants will be assigned a unique 
identifier that contains no protected health information. Access to the identifiers of the 
coded data will be controlled by the PI and only study team members will have access to the 
electronic and paper data. All members of the study team will undergo Human Subjects 
Research training. 
All adverse events will be reported in accordance with IRB and NIH requirements. 
All risks and alternative treatment options will be explicitly stated in consent documents. 
8.4.3 Potential Benefits of Trial Participation 
It is unknown whether the functional mobility of the participants will improve as a 
result of study participation, but evidence suggests that greater physical activity leads to 
improved motor performance. The results of the pilot study and outcomes of conventional 
early intervention rehabilitation also suggest that at least modest gains can be expected from 
participation in either rehabilitation treatment. The knowledge gained will inform early 
rehabilitation practice for other children with CP and other neurodevelopmental conditions, 
may lead to the development of other interventions, and the risk to participants is minimal.  

 
 
 
 
 
 
19 
8.4.4 Risk-Benefit Assessment 
If the study hypotheses are supported, there will be implications for the rehabilitation 
of individuals with CP and other neurodevelopmental conditions, and the results will likely 
lead to the development of other interventions, including those that can by conducted in the 
home and smaller clinical settings. This knowledge is important because CP is the most 
common cause of physical disability in children, affecting over 10,000 babies each year in 
the United States, and few interventions exist for meaningful functional improvement. The 
15 million individuals who live with CP worldwide experience this physical disability for 
their entire lifespan. There is no more than minimal risk to study participants, with the 
potential to learn important information about how to optimize motor development potential 
in young children with neurological injury. Therefore, the risk to potential benefit ratio for 
the proposed study is very small, and the potential importance is high. 
8.5 Recruitment Strategy 
Our goal is to enroll 16 and 20 participants in Years 1 and 2, respectively. The primary 
avenue for recruitment will be through the Neonatal Follow-up clinic at CHOP, directed by 
Dr. Bernbaum. Eligible patients seen in CHOP’s CP clinic and those with CP who are 
receiving services at the Center for Rehabilitation will also be invited to participate. 
Potential candidates who are not CHOP patients will be reached through the internet 
(www.clinicaltrials.gov 
and 
the 
CHOP 
Research 
Institute 
website 
http://www.research.chop.edu/research/clinical_research/) and mailings to local clinicians, 
including therapists, developmental pediatricians, and pediatric neurologists. All recruitment 
materials will receive prior ethics approval. 
We will also be working with the Recruitment Enhancement Core, including posting 
messages in the "This Week at CHOP" email to employees. Additionally, we will also work 
with the National Rehabilitation Information Center (NARIC) to send out notifications 
regarding our study. For both the "This Week at CHOP" and NARIC postings, we will use 
the approved blurb below in Section 7.01 (5.0) that is currently used on CHOP's public 
website. 
We will also work with PeRC to distribute mailings to potential participants.  PeRC 
will provide the study team with a list of names and contact information for mailings. 
Potential participants will be asked to call or email a member of the study team for 
additional information.  Interested participants will be contacted via phone or email for a 
information about the study. 
We will also work with Research Communications to create a short video about our 
study. This video will be distributed to rehabilitation therapists and early intervention 
agencies at CHOP and in the community outside of CHOP. This video can be shared with 
colleagues and/or caregivers of potential participants.  
8.6 Informed Consent/Assent and HIPAA Authorization 
A parent or legal representative of each potential participant will receive a verbal and 
written explanation of the purposes, procedures and risks of the study. If they are interested, 
the child will be scheduled for an initial physical therapy examination with the primary 

 
 
 
 
 
 
20 
research physical therapist. The therapist will conduct an examination to determine if the 
child meets the selection criteria. If eligible, the family will have the option to consider 
participation and later inform the therapist if they choose to participate, or they will be able 
to sign the informed consent documents at that time. Informed consent will be obtained by 
the research physical therapist, the trained study coordinator, or an investigator, and will be 
documented in the electronic database. The family will have the opportunity to ask questions 
throughout the entire process. The parent or legal representative must provide written 
informed consent prior to the start of any study activities. Written assents of minors will not 
be obtained due to the age of the participants. 
 
8.7 Payment to Subjects/Families 
8.7.1 Reimbursement for travel, parking and meals 
 
To encourage attendance at scheduled appointments, caregivers of participants will 
receive $5 per session to reduce their transportation cost burden (which is $3 parking for 
patients and $2 fuel, or public transportation for the participant and a caregiver at $3.10 
round trip per person within the city). This will be applicable to all visits, including both 
treatment and assessment sessions. Payment will be made through the ClinCard participant 
incentive program supported by the Research Institute.  
8.7.2 Payments to parent for time and inconvenience (i.e. compensation) 
Caregivers of participants will additionally receive $25 for completion of each of the 8 
assessments, including all applicable measures. Payment will be made through the ClinCard 
participant incentive program supported by the Research Institute. 
8.7.3 Payments to subject for time, effort and inconvenience (i.e. compensation) 
In accordance with CHOP patient incentive guidelines, no monetary payment will be 
made to participants as they will be between 1-3 years of age.   
8.7.4 Gifts 
 
Participants will receive small tokens of appreciation for participation throughout the 
study, such as stickers, stuffed animal or other small toys.  
 
9 
PUBLICATION 
Outcomes will be disseminated to various stakeholders, including pediatric and 
neurologic clinicians, rehabilitation researchers and parents. Examples of peer-reviewed 
scientific 
publications 
include 
 
Developmental 
Medicine 
& 
Child 
Neurology, 
Neurorehabilitation and Neural Repair, Physical Therapy, and Gait & Posture. 
 

 
 
 
 
 
 
21 
10 REFERENCES 
1. 
Rosenbaum P, Paneth N, Leviton A, et al. A report: the definition and classification of cerebral 
palsy April 2006. Dev Med Child Neurol Suppl. Feb 2007;109:8-14. 
2. 
Turk MA. Health, mortality, and wellness issues in adults with cerebral palsy. Dev Med Child 
Neurol. Oct 2009;51 Suppl 4:24-29. 
3. 
Pakula AT, Van Naarden Braun K, Yeargin-Allsopp M. Cerebral palsy: classification and 
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