Brain Damage, Chronic, Central Nervous System Diseases, Cerebral Palsy
Conditions
Keywords
muscle weakness, muscle power, resistance training, treadmill training
Brief summary
Ambulatory children with cerebral palsy (CP) experience walking limitations which negatively influence their ability to physically participate in day to day life. The investigators propose that impaired muscle power generation is the key limiting factor affecting walking activity and participation. This proposal represents a combined approach where participants undergo resistance training for muscle power generation in combination with locomotor treadmill training that is based on typical pediatric walking and activity patterns rather than adult protocols, which are endurance or time-based. Therefore, the primary objective of this randomized controlled trial is to determine the effect of lower extremity Power Training combined with interval Treadmill Training (PT³) on functional walking capacity and community-based activity and participation in children with CP. We hypothesize that remediating the most pronounced muscle performance impairment (i.e., muscle power) with power training combined with a task- specific approach to walking that is developmentally appropriate will have a significant effect on walking capacity and performance.
Detailed description
The primary purpose of this randomized controlled trial is to test the effect of Power Training combined with interval Treadmill Training (PT³) on walking capacity and performance in children with CP with walking limitations. To identify key muscular mechanisms associated with improved walking mobility, the effects of PT³ on muscle performance and architecture will be examined. The premise of the PT³ protocol is that a combined impairment and task-specific approach that is developmentally appropriate and targets muscle power deficits specifically, is necessary to drive changes in both clinic and community-based walking activity. In this randomized multi-site clinical trial, 48 ambulatory participants with CP will receive either PT³ or an equivalent dosage of traditional strength training combined with traditional treadmill training (comparison group) for 24 sessions, 3 times per week for 8 weeks. Outcomes will be collected at baseline and immediately post-treatment. Short and long-term retention effects will be assessed at 2 and 6 months post.
Interventions
BEHAVIORALPower training combined with interval treadmill training
Training will consist of unilateral and bilateral leg presses, targeting the quadriceps, hip extensors, and plantarflexors according to resistance training guidelines for muscle power training. The interval treadmill training portion will include short-bursts (30 seconds) of high speed walking intervals alternating with 30 seconds of low to moderate speed walking for a total of 30 minutes. Participants will train 3 x per week for 8 weeks. Total duration of each session will be approximately 1 hour.
BEHAVIORALStrength training combined with traditional treadmill training
Training will consist of unilateral and bilateral leg presses, targeting the quadriceps, hip extensors, and plantarflexors following the dosing and resistance training guidelines for muscle strength. Traditional treadmill training will consist of walking at steady-state speeds for 30 minutes. Participants will train 3 x per week for 8 weeks. Total duration of each session will be approximately 1 hour.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Washington
Louisiana State University Health Sciences Center in New Orleans
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of bilateral spastic Cerebral Palsy (CP) * Age 10 to 17 years inclusive * GMFCS levels I, II, or III
Exclusion criteria
* Orthopedic or neurosurgery less than 12 months prior to enrollment * Injection therapies (phenol, botulinum toxin) less than 3 months prior to enrollment * Lacking greater than 25 degrees of knee extension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Self-selected Gait Speed (Normalized) | Baseline and immediate post training (8-10 weeks post baseline) | Calculated from the 10 meter walk test in meters/second at self-selected speed and then normalized by stature to yield non-dimensional units. Higher values represent faster gait speeds. |
| Change in Fast Gait Speed (Normalized) | Baseline and immediate post training (8-10 weeks post baseline) | Calculated from the 10 meter walk test in meters/second at fast walking speed and then normalized by stature to yield non-dimensional units. Higher values equal faster gait speeds. |
| Change in Peak Power | Baseline and immediate post training (8-10 weeks post baseline) | Lower extremity peak power produced during a power leg press test averaged over 5 trials; product of force x velocity; adjusted for sled angle and body mass |
| Change in Average Strides Per Day | Baseline and immediate post training (8-10 weeks post baseline) | Average number of strides walked per day captured by Step Watch accelerometer as worn for a minimum of 4 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in One Minute Walk Test | Baseline and immediate post training (8-10 weeks post baseline) | Distance covered while walking as fast as possible for 1 minute measured in meters |
| Change in Cross-sectional Area | Baseline and immediate post training (8-10 weeks post baseline) | Cross-sectional area of rectus femoris taken at 50% distance between anterior superior iliac spine and apex of patella using 2D Bmode Ultrasound imaging in cm\^2; Average of Right and Left Sides |
| Change in Isokinetic Muscle Strength of Knee Extensors | Baseline and immediate post training (8-10 weeks post baseline) | Isokinetic dynamometer (Biodex System 3/4) according to published standard procedures for isokinetic strength. Calculated for knee extensors at 60 degrees/second in newton-meters |
| Change in Self-selected Gait Speed (Normalized) | Baseline and 2 months post training (16 weeks post baseline) | Calculated from the 10 meter walk test in meters/second at self-selected speed and then normalized by stature to yield non-dimensional units. Higher values equal faster speeds. |
| Change in Patient-Reported Outcomes Measurement Information System Physical Function-Mobility (PROMIS v2.0 Pediatric Profile 49 - Physical Function-Mobility) | Baseline and immediate post training (8-10 weeks post baseline) | Patient-Reported Outcomes Measurement Information System (PROMIS); The PROMIS item bank was developed from patient-reported outcome measures that indicate patients' state of well-being and functional abilities. The results of the Physical Function-Mobility domain are reported here as the Change in the T-score from baseline to 8-10wks post baseline. The T-score is a standardized T-score with a mean of 50 and a standard deviation (SD) of 10. Therefore, a person with a T-score of 40 is one SD below the mean. A higher PROMIS T-score represents more of the concept being measured so for a positive concept, such as Physical Function-Mobility, a higher T-score or 'change' in the T-score represents higher physical functioning and mobility. |
| Change in 1RM (Muscle Strength) | Baseline and immediate post training (8-10 weeks post baseline) | 1repetition maximum (1RM) testing on a leg press reported in lbs; external load reported after adjusting for the angle of the press |
| Change in Walking Intensity at Medium and High Stride Rates (Strides/Minute) | Baseline and immediate post training (8-10 weeks post baseline) | Average strides/day at medium (31 to 60 stride/min) and high (\> 60 stride/min) stride rates as captured by Step Watch accelerometer as worn for a minimum of 4 days |
| Change in Fast Gait Speed (Normalized) | Baseline and 2 months post training (16 weeks post baseline) | Calculated from the 10 meter walk test in meters/second at fast walking speed and then normalized by stature to yield non-dimensional units. Higher values equal faster speeds. |
| Change in Peak Power | Baseline and 2 months post training (16 weeks post baseline) | Lower extremity peak power produced during a power leg press test averaged over 5 trials; product of force x velocity; adjusted for sled angle and body mass |
| Change in Average Strides Per Day | Baseline and 2 months post training (16 weeks post baseline) | Average number of strides walked per day captured by Step Watch accelerometer as worn for a minimum of 4 days |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at two sites (academic medical center and a children's hospital). Participants were recruited from the surrounding community and regional tertiary pediatric care centers.
Pre-assignment details
Of the 44 enrolled participants, 43 were randomized. 1 participant was excluded prior to randomization due to the inability to cooperate and complete baseline assessments.
Participants by arm
| Arm | Count |
|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) Power Training combined with interval treadmill training
Power training combined with interval treadmill training: Training will consist of unilateral and bilateral leg presses, targeting the quadriceps, hip extensors, and plantarflexors according to resistance training guidelines for muscle power training. The interval treadmill training portion will include short-bursts (30 seconds) of high speed walking intervals alternating with 30 seconds of low to moderate speed walking for a total of 30 minutes. Participants will train 3 x per week for 8 weeks. Total duration of each session will be approximately 1 hour. | 23 |
| Traditional Training (Strength Training Combined With Treadmill Training) Strength training combined with traditional treadmill training
Strength training combined with traditional treadmill training: Training will consist of unilateral and bilateral leg presses, targeting the quadriceps, hip extensors, and plantarflexors following the dosing and resistance training guidelines for muscle strength. Traditional treadmill training will consist of walking at steady-state speeds for 30 minutes. Participants will train 3 x per week for 8 weeks. Total duration of each session will be approximately 1 hour. | 20 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Primary Endpoint - Immediate Post | PI decision; unable to perform exercises | 1 | 0 |
| Primary Endpoint - Immediate Post | Withdrawal by Subject | 2 | 1 |
| Primary Endpoint - Immediate Post | Withdrawn; COVID-19 shut down | 0 | 1 |
Baseline characteristics
| Characteristic | PT³ (Power Training Combined With Interval Treadmill Training) | Traditional Training (Strength Training Combined With Treadmill Training) | Total |
|---|---|---|---|
| Age, Continuous | 13.07 years STANDARD_DEVIATION 2.18 | 13.77 years STANDARD_DEVIATION 2.55 | 13.39 years STANDARD_DEVIATION 2.36 |
| Body mass | 44.43 kilograms (kg) STANDARD_DEVIATION 12.22 | 48.40 kilograms (kg) STANDARD_DEVIATION 19.86 | 46.28 kilograms (kg) STANDARD_DEVIATION 16.15 |
| Enrollment Site LSUHSC | 11 Participants | 10 Participants | 21 Participants |
| Enrollment Site SCRI | 12 Participants | 10 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 17 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| GMFCS Level GMFCS Level I | 5 Participants | 7 Participants | 12 Participants |
| GMFCS Level GMFCS Level II | 14 Participants | 12 Participants | 26 Participants |
| GMFCS Level GMFCS Level III | 4 Participants | 1 Participants | 5 Participants |
| Height | 1.50 meters STANDARD_DEVIATION 0.12 | 1.53 meters STANDARD_DEVIATION 0.15 | 1.516 meters STANDARD_DEVIATION 0.14 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 13 Participants | 15 Participants | 28 Participants |
| Region of Enrollment United States | 23 participants | 20 participants | 43 participants |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 11 Participants | 12 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 20 |
| other Total, other adverse events | 7 / 23 | 9 / 20 |
| serious Total, serious adverse events | 1 / 23 | 0 / 20 |
Outcome results
Primary
Change in Average Strides Per Day
Average number of strides walked per day captured by Step Watch accelerometer as worn for a minimum of 4 days
Time frame: Baseline and immediate post training (8-10 weeks post baseline)
Population: The a priori analytic approach included all participants in the primary analysis with the first (baseline) and second assessments.~LS Means adjusted for 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Average Strides Per Day | -95.84 strides/day | Standard Error 284.85 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Average Strides Per Day | -16.03 strides/day | Standard Error 318.79 |
Primary
Change in Fast Gait Speed (Normalized)
Calculated from the 10 meter walk test in meters/second at fast walking speed and then normalized by stature to yield non-dimensional units. Higher values equal faster gait speeds.
Time frame: Baseline and immediate post training (8-10 weeks post baseline)
Population: The a priori analytic approach included all participants in the primary analysis with the first (baseline) and second assessments.~LS Means adjusted for baseline and 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Fast Gait Speed (Normalized) | 0.0204 dimensionless | Standard Error 0.0074 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Fast Gait Speed (Normalized) | 0.0093 dimensionless | Standard Error 0.008 |
Primary
Change in Peak Power
Lower extremity peak power produced during a power leg press test averaged over 5 trials; product of force x velocity; adjusted for sled angle and body mass
Time frame: Baseline and immediate post training (8-10 weeks post baseline)
Population: The a priori analytic approach included all participants in the primary analysis with the first (baseline) and second assessments.~LS Means adjusted for 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Peak Power | 71.21 watts | Standard Error 18.71 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Peak Power | 19.19 watts | Standard Error 19.83 |
Primary
Change in Self-selected Gait Speed (Normalized)
Calculated from the 10 meter walk test in meters/second at self-selected speed and then normalized by stature to yield non-dimensional units. Higher values represent faster gait speeds.
Time frame: Baseline and immediate post training (8-10 weeks post baseline)
Population: The a priori analytic approach included all participants in the primary analysis with the first (baseline) and second assessments.~Least squares (LS) means adjusted for baseline and 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Self-selected Gait Speed (Normalized) | -0.0010 dimensionless | Standard Error 0.0096 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Self-selected Gait Speed (Normalized) | 0.0163 dimensionless | Standard Error 0.01 |
Secondary
Change in 1RM (Muscle Strength)
1repetition maximum (1RM) testing on a leg press reported in lbs; external load reported after adjusting for the angle of the press
Time frame: Baseline and immediate post training (8-10 weeks post baseline)
Population: LS Means adjusted for baseline and 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in 1RM (Muscle Strength) | 54.568 lbs | Standard Error 13.031 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in 1RM (Muscle Strength) | 49.961 lbs | Standard Error 14.263 |
Secondary
Change in Average Strides Per Day
Average number of strides walked per day captured by Step Watch accelerometer as worn for a minimum of 4 days
Time frame: Baseline and 2 months post training (16 weeks post baseline)
Population: LS Means adjusted for 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Average Strides Per Day | -139.77 strides/day | Standard Error 324.13 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Average Strides Per Day | -299.82 strides/day | Standard Error 373.2 |
Secondary
Change in Cross-sectional Area
Cross-sectional area of rectus femoris taken at 50% distance between anterior superior iliac spine and apex of patella using 2D Bmode Ultrasound imaging in cm\^2; Average of Right and Left Sides
Time frame: Baseline and immediate post training (8-10 weeks post baseline)
Population: LS Means adjusted for 3 covariates (Age group; Site; GMFCS level) and side tested (left and right)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Cross-sectional Area | 0.3390 cm^2 | Standard Error 0.0667 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Cross-sectional Area | 0.2692 cm^2 | Standard Error 0.0684 |
Secondary
Change in Fast Gait Speed (Normalized)
Calculated from the 10 meter walk test in meters/second at fast walking speed and then normalized by stature to yield non-dimensional units. Higher values equal faster speeds.
Time frame: Baseline and 2 months post training (16 weeks post baseline)
Population: LS Means adjusted for baseline and 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Fast Gait Speed (Normalized) | 0.0528 dimensionless | Standard Error 0.0125 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Fast Gait Speed (Normalized) | 0.0226 dimensionless | Standard Error 0.0127 |
Secondary
Change in Isokinetic Muscle Strength of Knee Extensors
Isokinetic dynamometer (Biodex System 3/4) according to published standard procedures for isokinetic strength. Calculated for knee extensors at 60 degrees/second in newton-meters
Time frame: Baseline and immediate post training (8-10 weeks post baseline)
Population: LS means adjusted for 3 covariates (Age group; Site; GMFCS level) and side tested (left and right)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Isokinetic Muscle Strength of Knee Extensors | 3.8778 Nm | Standard Error 3.0255 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Isokinetic Muscle Strength of Knee Extensors | 2.1524 Nm | Standard Error 3.1937 |
Secondary
Change in One Minute Walk Test
Distance covered while walking as fast as possible for 1 minute measured in meters
Time frame: Baseline and immediate post training (8-10 weeks post baseline)
Population: LS Means adjusted for baseline and 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in One Minute Walk Test | 8.349 meters | Standard Error 2.637 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in One Minute Walk Test | 7.750 meters | Standard Error 2.764 |
Secondary
Change in Patient-Reported Outcomes Measurement Information System Physical Function-Mobility (PROMIS v2.0 Pediatric Profile 49 - Physical Function-Mobility)
Patient-Reported Outcomes Measurement Information System (PROMIS); The PROMIS item bank was developed from patient-reported outcome measures that indicate patients' state of well-being and functional abilities. The results of the Physical Function-Mobility domain are reported here as the Change in the T-score from baseline to 8-10wks post baseline. The T-score is a standardized T-score with a mean of 50 and a standard deviation (SD) of 10. Therefore, a person with a T-score of 40 is one SD below the mean. A higher PROMIS T-score represents more of the concept being measured so for a positive concept, such as Physical Function-Mobility, a higher T-score or 'change' in the T-score represents higher physical functioning and mobility.
Time frame: Baseline and immediate post training (8-10 weeks post baseline)
Population: Least squares (LS) means adjusted for 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Patient-Reported Outcomes Measurement Information System Physical Function-Mobility (PROMIS v2.0 Pediatric Profile 49 - Physical Function-Mobility) | 2.229 T-score | Standard Error 1.72 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Patient-Reported Outcomes Measurement Information System Physical Function-Mobility (PROMIS v2.0 Pediatric Profile 49 - Physical Function-Mobility) | 2.792 T-score | Standard Error 1.83 |
Secondary
Change in Peak Power
Lower extremity peak power produced during a power leg press test averaged over 5 trials; product of force x velocity; adjusted for sled angle and body mass
Time frame: Baseline and 2 months post training (16 weeks post baseline)
Population: LS Means adjusted for 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Peak Power | 57.9248 watts | Standard Error 22.3544 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Peak Power | 1.5342 watts | Standard Error 23.4939 |
Secondary
Change in Self-selected Gait Speed (Normalized)
Calculated from the 10 meter walk test in meters/second at self-selected speed and then normalized by stature to yield non-dimensional units. Higher values equal faster speeds.
Time frame: Baseline and 2 months post training (16 weeks post baseline)
Population: LS Means adjusted for baseline and 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Self-selected Gait Speed (Normalized) | 0.0156 dimensionless | Standard Error 0.0092 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Self-selected Gait Speed (Normalized) | 0.0144 dimensionless | Standard Error 0.0092 |
Secondary
Change in Walking Intensity at Medium and High Stride Rates (Strides/Minute)
Average strides/day at medium (31 to 60 stride/min) and high (\> 60 stride/min) stride rates as captured by Step Watch accelerometer as worn for a minimum of 4 days
Time frame: Baseline and immediate post training (8-10 weeks post baseline)
Population: LS Means adjusted for 3 covariates (Age group; Site; GMFCS level)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PT³ (Power Training Combined With Interval Treadmill Training) | Change in Walking Intensity at Medium and High Stride Rates (Strides/Minute) | 0.01313 strides/minute | Standard Error 0.0289 |
| Traditional Training (Strength Training Combined With Treadmill Training) | Change in Walking Intensity at Medium and High Stride Rates (Strides/Minute) | -0.06635 strides/minute | Standard Error 0.0323 |