Effectiveness of Robotic Gait Training and Physical Therapy for Children and Youth With Cerebral Palsy

Cerebral palsy (CP) is the most common cause of childhood physical disability, affecting
2.0-2.5 in 1000 children. CP represents a group of disorders of movement and posture with
impairments (e.g., muscle weakness, decreased selective motor control, alterations in muscle
tone, and impairment of postural control) that collectively affect functional mobility. About
65% of children/youth with CP use minimal or no assistive devices (leg braces, walkers,
and/or wheelchairs) to walk (i.e., Gross Motor Function Classification System (GMFCS) Levels
I and II) while children in GMFCS Levels III - V require varying degrees of bracing, walkers
and other walking devices, wheelchairs, or assistance from others for mobility.

Robotic Assisted Gait training devices are increasingly used with children with CP to improve
their gait related motor skills. The Lokomat® (LOK) is a commercially available robot
assisted gait training system that uses robotics to simulate walking. It facilitates
inter-limb co-ordination and gait cycle timing and provides variable degrees of body weight
support and guidance.

This study represents the first adequately powered RCT to evaluate the effectiveness of robot
assisted gait training for children with CP. The qualitative aspect will give contextual
information to assist with interpretation of the RCT and provide valuable information about
families' experiences with the interventions.

The research questions for this study are:

i) What is the comparative effectiveness of robot assisted gait training (LOK) and fPT
program for improving gait related motor skills of ambulatory children and youth with CP? ii)
Does combining LOK and fPT result in greater improvements in gait related motor skills of
ambulatory children and youth with CP than robot assisted gait training or fPT alone? iii)
What are families' experiences with trial participation and what implications do they have
for interpretation of the quantitative results and the use of robot assisted gait training
and fPT in clinical settings?

Methods This trial is a concurrent, mixed methods study. Specifically, the quantitative arm
is a multi-centre RCT with four groups (22 factorial design, i.e., LOK absent/present, fPT
absent/present) with two periods of post-intervention assessments (immediate and 3 months
later). The RCT is linked with an interpretive descriptive qualitative study arm. The three
study sites are Holland Bloorview (Toronto, Ontario, Canada), Glenrose Rehabilitation
Hospital (Edmonton, Alberta, Canada) and Rehabilitation Institute of Chicago (Chicago, IL).

Participants - Children aged 5-18 with CP, GMFCS levels II and III. Inclusion/Exclusion
criteria included in protocol in documents section.

Randomization - Following the baseline assessment, participants will be randomly allocated to
one of the four groups using computer-generated random sequence.

Blinding Physical therapist assessors and data analysts will be blinded to group allocation.

TreatmentThere are three intervention groups: 1) LOK, 2) LOK + fPT, 3) fPT, and 4) one
maintenance therapy control (CONT) arm. All three intervention groups will receive two
50-minute sessions per week, conducted over 8 -10 weeks. Children in all four groups can
continue to participate in 'maintenance therapy'. Each child will be assigned to a treatment
team of two trained PTs who will share responsibility for the 8 to 10 week intervention
phase.

LOK - two 50-minute sessions on the Lokomat® per week. The study manualized LOK walking
protocol provides methods for progressing/tracking including a 5-minute over ground walking
session after the LOK to facilitate transfer of motor learning from the Lokomat to usual
walking devices.

fPT Participants will Two 50-minute sessions per week. The manualized motor-learning based
protocol forms the basis for this intervention. Its focus is on balance and multi-plane
gait-based motor skills.

LOK + fPT group protocol: Participants will alternate between LOK and one fPT session per
week for the duration of the 8 to 10 week intervention phase.

Monitoring co-interventionsMaintenance therapies such as home stretching and strengthening
routines can be continued for all 4 groups throughout the study because these therapies have
questionable efficacy, and will likely be equally used across all four groups as they are
common PT recommendations.

Outcomes - All study outcomes will be measured pre-/post-intervention (< 10 days
pre-intervention and post-completion), and at 3m follow-up (+/- 10 day window) by trained
physical therapists. Data will be entered into REDCap.

Primary Outcome - The primary outcome measure is the Gross Motor Function Measure-66 (GMFM-66
Dimensions D (Stand) and E (Walk/Run/Jump).

Secondary Outcomes - Secondary outcomes are measures of walking capacity(6 minute walk test)
fitness (adapted shuttle run test), balance (Pediatric Berg Balance Scale, Quality Function
Measure (FM), and Activities Balance Confidence Scale), functional abilities (PEDI-CAT),
physical activity levels (accelerometry), participation (Participation and Environment
Measure for Children and Youth), physical activity self-efficacy (Self-Efficacy for Physical
Activity), individualized goal attainment (Canadian Occupational Performance Measure (COPM)
and Goal Attainment Scaling), and quality of life (KidScreen and Students' Life Satisfaction
Scale).

Statistical Analysis - Data will be described (e.g., means, standard deviations, frequencies)
for each intervention group and each stratification variable. Mixed-effects multiple linear
regression models will be developed for each outcome with centre as a random effect, centre
by intervention as an interaction (to assess centre effect), and other important variables
(e.g., age and GMFCS level) as covariates. All main analyses will be based on intent-to-treat
with secondary analyses of those with >80% adherence to their intervention.

Qualitative Component

The three objectives of the concurrent qualitative component are to explicate:

1. Child and parent experiences with the trial interventions and the values and previous
experiences that shape their perceptions.

2. The mobility related outcomes that are important to families and factors that influence
these views.

3. Child and family values, experiences and contextual factors that influenced
participation in the trial, including the follow-up period.

Design Interpretive description

Sample selection- The investigators will invite a subset of child-parent dyads from each of
the active interventions in the RCT. In addition, parents of children who were eligible but
declined to participate in the RCT will be invited to participate in the qualitative
component to address objective #3. The estimated sample size is (i.e., 6 child/parent dyads
plus 3 parents from each site).

Data Collection - Parents will participate in 45-60 minute semi-structured, individual
interviews conducted by one member of the research team. Participating parents of children in
the RCT will be interviewed at 2 points within the trial: i) after completion of the COPM and
prior to receiving the intervention, and ii) within one month of intervention completion.

Children from the RCT will participate in individual interviews at the end of their LOK/fPT
intervention. A customizable "tool box" of age-appropriate child-friendly techniques
including photographs and comic captioning, vignettes, and sentence starters will be used in
a 30-45 minute semi-structured interview with the child without the parent present.

Data Management and Analysis Interviews will be digitally audio-recorded, transcribed
verbatim by a professional transcriptionist, de-identified and imported into NVivo for data
management. Two researchers will collaboratively identify general coding categories. The
researchers will meet to establish consensus on the coding.

Inclusion Criteria:

- Diagnosis of CP (any type), GMFCS Levels II and III

- Able to follow GMFM testing instructions, and to participate in a minimum of 30
minutes of active PT (as judged by the child's PT or physician if not followed by a
PT)

- Able to reliably signal pain, fear and discomfort using verbal or nonverbal signals

- Passive range of motion (ROM) of hips and knees within minimum range requirement for
LOK (hip and knee flexion contracture < 10 degrees, and knee valgus < 40 degrees).

- Parent/child agrees to attend 16 study intervention sessions (given within two 10-week
periods), a LOK fitting/acclimatization session or fPT acclimatization session and the
three assessment sessions during the course of the study.

- Parent agrees to contact of their primary PT (if not already involved by parent in the
screening process) and their paediatrician or physiatrist to confirm eligibility.

- Parent agrees that regular PT (and other gross motor mobility therapies such as
conductive education and MEDEK) will be discontinued from the time of the baseline
assessment through the 8 to 10 weeks of the active intervention or control group. Note
that home programs such as stretching and strengthening and treadmill and exercise
bike riding (no more than 10 minutes total per day) will be permitted in all groups.

Exclusion Criteria:

- Botulinum Toxin injection within the past 4 months or planned within the next 6 months

- Fixed knee contracture > 10 degrees, knee valgus >40 degrees such that orthosis will
not be adaptable to lower limbs.

- Hip instability/subluxation as demonstrated by a migration percentage > 45%

- Orthopaedic surgery (soft tissue releases) within the last 9 months, or lower limb
bony surgery within the last 18 months

- Severe spasticity may be a contraindication as determined in Lokomat trial session
using L-FORCE assessment.

- Any weightbearing restrictions.

- Seizure disorder unless fully controlled by medication and no evidence of seizure in
the last 12 months and physician provides singed approval to enter the study

- Open skin lesions or vascular disorder of lower extremities

- Not able to co-operate or be positioned adequately within the LOK as shown during the
fitting/acclimatisation session. -