Cerebral Palsy, CP, Spastic Cerebral Palsy
Conditions
Keywords
Cerebral Palsy, CP, Spastic Cerebral Palsy, Cord Blood, Umbilical Cord Blood, Autologous Cord Blood
Brief summary
The purpose of this study is to determine the efficacy of a single intravenous infusion of autologous umbilical cord blood (UCB) for the treatment of pediatric patients with spastic cerebral palsy.
Detailed description
Cerebral palsy results from in utero or perinatal injury to the developing brain, often through stroke, hypoxic insult or hemorrhage. Currently available treatments for patients with cerebral palsy are supportive, but not curative. Umbilical cord blood (UCB) has been shown to lessen the clinical and radiographic impact of hypoxic brain injury and stroke in animal models. UCB also engrafts and differentiates in brain, facilitating neural cell repair, in animal models and human patients with inborn errors of metabolism undergoing allogeneic, unrelated donor UCB transplantation. We hypothesize that, in the setting of brain injury, infusion of autologous UCB will facilitate neural cell repair resulting in improved function in pediatric patients with cerebral palsy.
Interventions
BIOLOGICALAutologous UCB Reinfusion
Autologous umbilical cord blood (UCB) reinfusion
OTHERPlacebo
Placebo
Sponsors
Joanne Kurtzberg, MD
The Robertson Foundation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Months to 6 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 12 months and ≤ 6 years * Diagnosis: Spastic cerebral palsy with diplegia, hemiplegia, or quadraplegia. * Performance status: Gross Motor Function (GMF) Classification Score levels II - IV or GMF Score leve I, age \>/= 2 years Spastic hemiplegia: GMF Score II-IV or minimal functional capabilities in the affected upper extremity. A subject classified as GMFCS level I with significant upper extremity impairment will be eligible if the affected upper extremity is used as an assist only. An eligibility committee will meet to review the child's records and determine eligibility. Bilateral hypotonic CP (diplegia or quadriplegia): GMF Score II-IV and an abnormal brain MRI suggestive of an acquired etiology (versus a genetic etiology or brain malformation). * Autologous umbilical cord blood available at a private or public cord blood bank with a minimum total nucleated cell dose of ≥ 1 x 107 cells/kilogram. * Parental consent.
Exclusion criteria
* Athetoid cerebral palsy. * Autism and autistic spectrum disorders without motor disability. * Hypsarrhythmia. * Intractable seizures causing epileptic encephalopathy. * Evidence of a progressive neurologic disease. * Known HIV or uncontrolled bacterial, fungal, or viral infections. * Impaired renal or liver function as determined by serum creatinine \>1.5mg/dL and/or total bilirubin \>1.3mg/dL. * Head circumference \>3 standard deviations below the mean for age. * Known genetic disease or phenotypic evidence of a genetic disease on physical examination. * Concurrent genetic or acquired disease or comorbidity(ies) that could require a future allogeneic stem cell transplant. * Requires ventilatory support, including home ventilator, CPAP, BiPAP, or supplemental oxygen. * Patient's medical condition does not permit safe travel. * Previously received any form of cellular therapy. * Autologous umbilical cord blood unit has any of the following: 1. Total nuclear cell dose \< 1 x 107 cells/kilogram 2. Positive maternal infectious disease markers (except CMV) 3. Evidence of infectious contamination of the cord blood unit 4. Lack of a test sample to confirm identity 5. Evidence of a genetic disease * Unable to obtain parental consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gross Motor Function Measure 66 (GMFM-66) Score | Baseline to Year 1 | Change in Gross Motor Function Measure 66 (GMFM-66) Score from Baseline to Year 1. The GMFM-66 is a clinical tool used to evaluate gross motor function in children with cerebral palsy and is scored using a propriety software program called the Gross Motor Ability Estimator (GMAE) that produces an interval level continuous score ranging from 0 to 100. Higher scores indicate better motor function. A negative change in GMFM-66 score indicates a reduction in motor function, a positive change indicates improvement in motor function, and zero indicates no change in motor function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in IT-QOL Questionnaire Score | Baseline to Year 1 | The Infant and Toddler Quality of Life Questionnaire (IT-QOL) was utilized for children ages one to three years at study entry.This 97-item questionnaire is completed by the parents and covers 12 concepts related to the physical, mental, and social well being of the child and the impact of their illness on the family. Scores range from 0 (worst health) to 100 (best health). The change from Baseline to Year 1 is summarized here for each of the 12 items on the questionnaire. Negative values indicate a decline in quality of life over time, positive values indicate an improvement, and zero indicates no change. |
| Change in CP-QOL Score | Baseline, Year 1 | Children age four years or older at study entry were assessed using the disease-specific "CP-QOL Child" assessment tool as completed by a parent. The CP-QOL Child primary-caregiver proxy form is designed for children 4 - 12 with cerebral palsy and contains 66 items which assess physical, emotional, and social well being as well as access to services and acceptance by others. Scores are summarized in seven topic areas. Scores in each area range from 0 (worst health) to 100 (best health). The change score from Baseline to Year 1 is summarized here for each item. Negative scores indicated a decrease in quality of life, positive scores indicate an increase and zero indicates no change. |
| Change in Whole Brain Connectivity Measured by Diffusion Tensor Magnetic Resonance Imaging (MRI) | Baseline to Year 1 | Change in number of connections in the brain as measured by diffusion tensor magnetic resonance imaging (MRI). Changes in connectivity are normalized to white matter volume of the brain. A positive number indicates an increase in connections, a negative number indicates a decrease, and zero indicates no change. The number of connections is expressed in terms of 10e5. For example, a change of 1 indicates an increase of 1x10e5 or 100,000 connections. |
| Change in Loes Score of Functional MRI From Baseline to Year 1 and From Year 1 to Year 2 | Baseline, Year 1, Year 2 | No data were collected from this procedure because enrolled subjects who were eligible to receive fMRI were unable to comply with the procedure. |
| Change in Child Behavior Checklist (CBCL) Z-score Total Problems From Baseline to Year 1 | Baseline to Year 1 | Two versions of the CBCL exist for children ages 1.5 to 5 years and ages 6-18 years. The CBCL evaluates internalizing and externalizing behaviors and total problems using 99-item assessments that are scored on an ordinal scale as 0 for "not true of the child," 1 for "somewhat or sometimes true of the child," and 2 for "very true or often true of the child" based on behavior in the preceding two months. Scores are expressed on a standard normal distribution with mean 50 and standard deviation 10. Z scores were created for analysis. A Z-score represents the distance from the population mean in terms of the number of standard deviations. The change in Z-score from Baseline to Year 1 was calculated for each patient. A positive number indicates an increase in the behavior, a negative number indicates a decrease in the behavior, and a zero indicates no change. |
| Change in Bayley Scales of Infant and Toddler Development-III, Cognitive Composite From Baseline to Year 1 | Baseline to Year 1 | Cognitive function was assessed in English-speaking study participants using one of three different tools depending on the age of the patient at the time of assessment: The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Wechsler Intelligence Scale for Children (WISC-IV), and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Some patients were assessed with different tools at subsequent visits as they aged during the conduct of the trial. The Bayley-III is designed to assess developmental functioning of infants and toddlers. Scores for the Cognitive Composite range from 1 to 19 and results in the range of 8 to 12 are considered average. The outcome measure reported here is the change in Cognitive Composite between Baseline to Year 1. Positive numbers indicate increases in cognitive functioning, negative numbers indicate a decrease, and zero indicates no change. |
| Change in Parental Distress From Baseline to Year 1 | Baseline to Year 1 | Parent stress was evaluated with the Parenting Stress Index - Short Form for children aged 0-12 years, which measures stress in three domains: Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child. Results in each domain are expressed as percentiles. Scores from the 15th-80th percentile are considered to be within the normal range. Scores at or above the 85th percentile considered high distress. Scores greater than the 89th percentile indicate clinically significant levels of distress. Analysis focused on changes in percentile scores between Baseline and Year 1. Positive numbers represent an increase in distress, negative numbers represent a decrease in distress, and zero indicates no change. |
| Change in Parent-Child Dysfunctional Interaction From Baseline to Year 1 | Baseline to Year 1 | Parent stress was evaluated with the Parenting Stress Index - Short Form for children aged 0-12 years, which measures stress in three domains: Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child. Results in each domain are expressed as percentiles. Scores from the 15th-80th percentile are considered to be within the normal range. Scores at or above the 85th percentile considered high distress. Scores greater than the 89th percentile indicate clinically significant levels of distress. Analysis focused on changes in percentile scores between Baseline and Year 1. Positive numbers represent an increase in distress, negative numbers represent a decrease in distress, and zero indicates no change. |
| Change in Difficult Child Score From Baseline to Year 1 | Baseline to Year 1 | Parent stress was evaluated with the Parenting Stress Index - Short Form for children aged 0-12 years, which measures stress in three domains: Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child. Results in each domain are expressed as percentiles. Scores from the 15th-80th percentile are considered to be within the normal range. Scores at or above the 85th percentile considered high distress. Scores greater than the 89th percentile indicate clinically significant levels of distress. Analysis focused on changes in percentile scores between Baseline and Year 1. Positive numbers represent an increase in distress, negative numbers represent a decrease in distress, and zero indicates no change. |
| Modified Ashworth Scale at Baseline | Baseline | The Modified Ashworth Scale uses a 6 point scale (range 0, 1, 1+, 2, 3, or 4) to measure spasticity in 5 body regions (central, right upper extremity, left upper extremity, right lower extremity, and left lower extremity). Scores of 0 indicate no increase in muscle tone whereas a score of 4 indicates rigidity in flexion or extension. |
| Modified Ashworth Scale at Year 1 | Year 1 | The Modified Ashworth Scale uses a 6 point scale (range 0, 1, 1+, 2, 3, or 4) to measure spasticity in 5 body regions (central, right upper extremity, left upper extremity, right lower extremity, and left lower extremity). Scores of 0 indicate no increase in muscle tone whereas a score of 4 indicates rigidity in flexion or extension. |
| Change in Bruininks-Oseretsky-2 Total Motor Composite From Baseline to Year 1 | Baseline to Year 1 | The Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, (BOT-2) evaluates motor function in four areas: stability, mobility, strength, coordination, and object manipulation. A Total Motor Composite is then calculated and expressed on a normal distribution with mean 50 and standard deviation of 10. Higher scores indicate better motor function. The BOT-2 Total Motor Composite was used to measure motor function in children at age 6 in this study. The study intended to evaluate change in the BOT-2 Total Motor Composite from Baseline to Year 1, where positive change indicates improvement in motor function, negative change indicates decrease in motor function, and zero indicates no change. |
| Parent Experience of Child Illness (PECI) | Baseline to Year 1 | The PECI is a 25-item measure designed to examine parental adjustment related to caring for a chronically ill child. |
| Correlation Between Clinical Response and RNA Expression of Neural, Endothelial and Inflammatory Cytokines Measured by RNA Arrays in Cord Blood Cells Given to These Patients. | 2 years | Various pre-selected neural, angiogenic, and anti-inflammatory markers expressed by UCB cells and clinical response will be evaluated. |
| Change in Wechsler Preschool and Primary Scale of Intelligence (WPPSI) III Full Scale Intelligence Quotient (IQ) for Younger Children (Ages 2 Years & 6 Months to 3 Years & 11 Months) From Baseline to Year 1. | Baseline to Year 1 | Cognitive function was assessed in English-speaking study participants using one of three different tools depending on the age of the patient at the time of assessment: The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Wechsler Intelligence Scale for Children (WISC-IV), and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Some patients were assessed with different tools at subsequent visits as they aged during the conduct of the trial. There are two versions of the WPPSI-III for two different age ranges: 2 years \& 6 months to 3 years \& 11 months, and 4 years to 7 years \& 3 months. The Full Scale IQ is calculated for both age ranges and provides a continuous score with an average of 100 and a standard deviation of 15. Change from Baseline to Year 1 was evaluated, with positive numbers indicating an increase in cognitive ability, negative numbers indicating a decrease in cognitive ability, and zero indicating no change. |
| Change in the Wechsler Intelligence Scale for Children (WISC-IV) From Baseline to Year 1. | Baseline to Year 1 | Cognitive function was assessed in English-speaking study participants using one of three different tools depending on the age of the patient at the time of assessment: The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Wechsler Intelligence Scale for Children (WISC-IV), and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Some patients were assessed with different tools at subsequent visits as they aged during the conduct of the trial. The WISC-IV is designed for children 6 years 0 months to 16 years 11 months. This study used the Full Scale IQ, which ranges from 45 to 155 with a mean of 100 and standard deviation of 15. Higher scores indicate stronger cognitive function. Scores between 90 and 110 are considered to be within the range of average IQ. |
| Change in Cognitive Z-Score From Baseline to Year 1 | Baseline to Year 1 | Because patients in this study were evaluated with different cognitive assessments based on their age at the time of assessment (The Bayley-III Cognitive Composite, the WPSSI-III Full Scale IQ, and the WISC-IV Full Scale IQ Composite), with some patients being assessed using different tools at subsequent visits during the trial, a method for combining the assessments was employed to evaluate change in cognitive function over time in as many patients as possible. A cognitive Z-score was calculated for each participant at Baseline and Year 1 by adjusting each score by the relevant assessments' population mean and standard deviation. The Z-scores represent the distance from the population mean, as measured by standard deviations. The analysis presented here summarizes the change in Z-score between Baseline and Year 1. A positive number indicates an increase in cognitive function, a negative number indicates a decrease, and zero indicates no change. |
| Change in Assisting Hand Assessment (AHA) Score From Baseline to Year 1 | Baseline to Year 1 | The Assisting Hand Assessment (AHA) measures the use of hemiplegic cerebral palsy patients' involved hand in tasks involving two hands. The test is valid for ages 18 months to 12 years. The score is an interval scale ranging from 22 to 88 with higher numbers indicating more effective use of the affected hand in performance of bimanual tasks. Change in this score was evaluate between Baseline and Year 1. Positive numbers indicate more effective use of the affected hand, negative numbers indicate a reduction in the effective use of the affected hand, and a zero indicates no change. |
| Change in Pediatric Evaluation of Disability (PEDI) Self Care Score | Baseline to Year 1 | The Pediatric Evaluation of Disability is used to evaluate functional skills in children aged 6 months to 7 years in three areas: Self Care, Mobility, and Social Function. The score in each area can range from 10-90. Higher scores indicate higher function. The change from Baseline to Year 1 in the Self Care score is presented here. Positive scores indicate increased function, negative scores indicate a decrease, and zero indicates no change. |
| Change in Pediatric Evaluation of Disability (PEDI) Mobility Score | Baseline to Year 1 | The Pediatric Evaluation of Disability is used to evaluate functional skills in children aged 6 months to 7 years in three areas: Self Care, Mobility, and Social Function. The score in each area can range from 10-90. Higher scores indicate higher function. The change from Baseline to Year 1 in the Mobility score is presented here. Positive scores indicate increased function, negative scores indicate a decrease, and zero indicates no change. |
| Change in Pediatric Evaluation of Disability (PEDI) Social Function Score | Baseline to Year 1 | The Pediatric Evaluation of Disability is used to evaluate functional skills in children aged 6 months to 7 years in three areas: Self Care, Mobility, and Social Function. The score in each area can range from 10-90. Higher scores indicate higher function. The change from Baseline to Year 1 in the Social Function score is presented here. Positive scores indicate increased function, negative scores indicate a decrease, and zero indicates no change. |
| Change in Child Behavior Checklist (CBCL) Z-score Internalizing Problems From Baseline to Year 1 | Baseline to Year 1 | Two versions of the CBCL exist for children ages 1.5 to 5 years and ages 6-18 years. The CBCL evaluates internalizing and externalizing behaviors and total problems using 99-item assessments that are scored on an ordinal scale as 0 for "not true of the child," 1 for "somewhat or sometimes true of the child," and 2 for "very true or often true of the child" based on behavior in the preceding two months. Scores are expressed on a standard normal distribution with mean 50 and standard deviation 10. Z scores were created for analysis. A Z-score represents the distance from the population mean in terms of the number of standard deviations. The change in Z-score from Baseline to Year 1 was calculated for each patient. A positive number indicates an increase in the behavior, a negative number indicates a decrease in the behavior, and a zero indicates no change. |
| Change in Peabody Gross Motor Quotient From Baseline to Year 1 | Baseline to Year 1 | The Peabody Developmental Motor Scales - Second Edition (PDMS-2) measures gross and fine motor skills in children from birth through five years of age. The Gross Motor Quotient score from the PDMS-2 was used in this study to evaluate gross motor function. The Gross Motor Quotient measures the ability to use large muscle systems for locomotion, maintain a stable posture when not moving, and throw/catch objects. The range of possible scores is 41 to 164. High scores indicate better gross motor function. Lower scores indicate less gross motor function ability. The change in Gross Motor Quotient from Baseline to Year 1 was evaluated in this study. Positive numbers indicate an increase in gross motor ability, negative numbers indicate decreases in gross motor function, and a zero indicates no change. |
| Change in Child Behavior Checklist (CBCL) Z-score Externalizing Problems From Baseline to Year 1 | Baseline to Year 1 | Two versions of the CBCL exist for children ages 1.5 to 5 years and ages 6-18 years. The CBCL evaluates internalizing and externalizing behaviors and total problems using 99-item assessments that are scored on an ordinal scale as 0 for "not true of the child," 1 for "somewhat or sometimes true of the child," and 2 for "very true or often true of the child" based on behavior in the preceding two months. Scores are expressed on a standard normal distribution with mean 50 and standard deviation 10. Z scores were created for analysis. A Z-score represents the distance from the population mean in terms of the number of standard deviations. The change in Z-score from Baseline to Year 1 was calculated for each patient. A positive number indicates an increase in the behavior, a negative number indicates a decrease in the behavior, and a zero indicates no change. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJoanne Kurtzberg, MD
Duke University
Participant flow
Pre-assignment details
Participants were enrolled and randomized on the same day.
Participants by arm
| Arm | Count |
|---|---|
| Autologous UCB First, Then Placebo Subjects receive autologous umbilical cord blood at Baseline, then Placebo at Year 1. | 32 |
| Placebo First, Then Autologous UCB Reinfusion Subjects receive Placebo at Baseline, then autologous umbilical cord blood at Year 1. | 31 |
| Total | 63 |
Baseline characteristics
| Characteristic | Autologous UCB First, Then Placebo | Total | Placebo First, Then Autologous UCB Reinfusion |
|---|---|---|---|
| Age, Continuous | 2.1 Years | 2.3 Years | 2.3 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 56 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| GMFCS Level Level I | 11 Participants | 17 Participants | 6 Participants |
| GMFCS Level Level II | 9 Participants | 24 Participants | 15 Participants |
| GMFCS Level Level III | 4 Participants | 8 Participants | 4 Participants |
| GMFCS Level Level IV | 8 Participants | 14 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 55 Participants | 28 Participants |
| Sex: Female, Male Female | 12 Participants | 21 Participants | 9 Participants |
| Sex: Female, Male Male | 20 Participants | 42 Participants | 22 Participants |
| Type of Cerebral Palsy Hypotonic Quadriplegia | 1 Participants | 4 Participants | 3 Participants |
| Type of Cerebral Palsy Spastic Diplegia | 6 Participants | 12 Participants | 6 Participants |
| Type of Cerebral Palsy Spastic Hemiplegia | 15 Participants | 30 Participants | 15 Participants |
| Type of Cerebral Palsy Spastic Quadriplegia | 10 Participants | 17 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 63 |
| other Total, other adverse events | 24 / 63 | 4 / 63 |
| serious Total, serious adverse events | 0 / 63 | 1 / 63 |
Outcome results
Primary
Change in Gross Motor Function Measure 66 (GMFM-66) Score
Change in Gross Motor Function Measure 66 (GMFM-66) Score from Baseline to Year 1. The GMFM-66 is a clinical tool used to evaluate gross motor function in children with cerebral palsy and is scored using a propriety software program called the Gross Motor Ability Estimator (GMAE) that produces an interval level continuous score ranging from 0 to 100. Higher scores indicate better motor function. A negative change in GMFM-66 score indicates a reduction in motor function, a positive change indicates improvement in motor function, and zero indicates no change in motor function.
Time frame: Baseline to Year 1
Population: All enrolled patients were analyzed as randomized from Baseline to Year 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Gross Motor Function Measure 66 (GMFM-66) Score | 7.5 units on a scale | Standard Deviation 6.8 |
| Placebo First, Then Autologous UCB Reinfusion | Change in Gross Motor Function Measure 66 (GMFM-66) Score | 6.9 units on a scale | Standard Deviation 5.6 |
Comparison: H0: The true mean 1-year change in GMFM-66 is the same on Autologous Umbilical Cord Blood and Placebop-value: 0.7295% CI: [-2.6, 3.7]t-test, 2 sided
Secondary
Change in Assisting Hand Assessment (AHA) Score From Baseline to Year 1
The Assisting Hand Assessment (AHA) measures the use of hemiplegic cerebral palsy patients' involved hand in tasks involving two hands. The test is valid for ages 18 months to 12 years. The score is an interval scale ranging from 22 to 88 with higher numbers indicating more effective use of the affected hand in performance of bimanual tasks. Change in this score was evaluate between Baseline and Year 1. Positive numbers indicate more effective use of the affected hand, negative numbers indicate a reduction in the effective use of the affected hand, and a zero indicates no change.
Time frame: Baseline to Year 1
Population: Participants who were less than 18 months old, or had diplegia or quadriplegia were excluded. For those with unspecified typography, AHA scores were excluded if scores on either the Modified Ashworth Scale or Barry-Albright Dystonia scale indicated neither or both of the upper extremities were involved.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Assisting Hand Assessment (AHA) Score From Baseline to Year 1 | 5.4 units on a scale | Standard Error 2.1 |
| Placebo First, Then Autologous UCB Reinfusion | Change in Assisting Hand Assessment (AHA) Score From Baseline to Year 1 | 5.1 units on a scale | Standard Error 2.3 |
p-value: 0.912t-test, 2 sided
Secondary
Change in Bayley Scales of Infant and Toddler Development-III, Cognitive Composite From Baseline to Year 1
Cognitive function was assessed in English-speaking study participants using one of three different tools depending on the age of the patient at the time of assessment: The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Wechsler Intelligence Scale for Children (WISC-IV), and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Some patients were assessed with different tools at subsequent visits as they aged during the conduct of the trial. The Bayley-III is designed to assess developmental functioning of infants and toddlers. Scores for the Cognitive Composite range from 1 to 19 and results in the range of 8 to 12 are considered average. The outcome measure reported here is the change in Cognitive Composite between Baseline to Year 1. Positive numbers indicate increases in cognitive functioning, negative numbers indicate a decrease, and zero indicates no change.
Time frame: Baseline to Year 1
Population: The Bayley III is an age-specific test and was used for 42 patients at Baseline. A total of 27 of these patients were also scored with the Bayley III at Year 1. The results here represent change from Baseline to Year 1 in the 27 participants assessed with the Bayley III at both time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Bayley Scales of Infant and Toddler Development-III, Cognitive Composite From Baseline to Year 1 | 3.2 units on a scale | Standard Error 3 |
| Placebo First, Then Autologous UCB Reinfusion | Change in Bayley Scales of Infant and Toddler Development-III, Cognitive Composite From Baseline to Year 1 | 8.1 units on a scale | Standard Error 3.3 |
p-value: 0.29t-test, 2 sided
Secondary
Change in Bruininks-Oseretsky-2 Total Motor Composite From Baseline to Year 1
The Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, (BOT-2) evaluates motor function in four areas: stability, mobility, strength, coordination, and object manipulation. A Total Motor Composite is then calculated and expressed on a normal distribution with mean 50 and standard deviation of 10. Higher scores indicate better motor function. The BOT-2 Total Motor Composite was used to measure motor function in children at age 6 in this study. The study intended to evaluate change in the BOT-2 Total Motor Composite from Baseline to Year 1, where positive change indicates improvement in motor function, negative change indicates decrease in motor function, and zero indicates no change.
Time frame: Baseline to Year 1
Population: The BOT-2 Total Motor Composite was available at Baseline and Year 1 in only 1 subject. The change score for that subject is reported here.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Bruininks-Oseretsky-2 Total Motor Composite From Baseline to Year 1 | -1 units on a scale |
Secondary
Change in Child Behavior Checklist (CBCL) Z-score Externalizing Problems From Baseline to Year 1
Two versions of the CBCL exist for children ages 1.5 to 5 years and ages 6-18 years. The CBCL evaluates internalizing and externalizing behaviors and total problems using 99-item assessments that are scored on an ordinal scale as 0 for not true of the child, 1 for somewhat or sometimes true of the child, and 2 for very true or often true of the child based on behavior in the preceding two months. Scores are expressed on a standard normal distribution with mean 50 and standard deviation 10. Z scores were created for analysis. A Z-score represents the distance from the population mean in terms of the number of standard deviations. The change in Z-score from Baseline to Year 1 was calculated for each patient. A positive number indicates an increase in the behavior, a negative number indicates a decrease in the behavior, and a zero indicates no change.
Time frame: Baseline to Year 1
Population: Evaluations done outside the age ranges specified for the assessments were excluded, the majority being assessments that were done on patients who were not yet 1.5 years of age.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Child Behavior Checklist (CBCL) Z-score Externalizing Problems From Baseline to Year 1 | -0.2 units on a scale | Standard Error 0.2 |
| Placebo First, Then Autologous UCB Reinfusion | Change in Child Behavior Checklist (CBCL) Z-score Externalizing Problems From Baseline to Year 1 | 0.1 units on a scale | Standard Error 0.1 |
p-value: 0.099t-test, 2 sided
Secondary
Change in Child Behavior Checklist (CBCL) Z-score Internalizing Problems From Baseline to Year 1
Two versions of the CBCL exist for children ages 1.5 to 5 years and ages 6-18 years. The CBCL evaluates internalizing and externalizing behaviors and total problems using 99-item assessments that are scored on an ordinal scale as 0 for not true of the child, 1 for somewhat or sometimes true of the child, and 2 for very true or often true of the child based on behavior in the preceding two months. Scores are expressed on a standard normal distribution with mean 50 and standard deviation 10. Z scores were created for analysis. A Z-score represents the distance from the population mean in terms of the number of standard deviations. The change in Z-score from Baseline to Year 1 was calculated for each patient. A positive number indicates an increase in the behavior, a negative number indicates a decrease in the behavior, and a zero indicates no change.
Time frame: Baseline to Year 1
Population: Evaluations done outside the age ranges specified for the assessments were excluded, the majority being assessments that were done on patients who were not yet 1.5 years of age.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Child Behavior Checklist (CBCL) Z-score Internalizing Problems From Baseline to Year 1 | -0.6 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in Child Behavior Checklist (CBCL) Z-score Internalizing Problems From Baseline to Year 1 | 0.0 units on a scale |
p-value: 0.176Wilcoxon (Mann-Whitney)
Secondary
Change in Child Behavior Checklist (CBCL) Z-score Total Problems From Baseline to Year 1
Two versions of the CBCL exist for children ages 1.5 to 5 years and ages 6-18 years. The CBCL evaluates internalizing and externalizing behaviors and total problems using 99-item assessments that are scored on an ordinal scale as 0 for not true of the child, 1 for somewhat or sometimes true of the child, and 2 for very true or often true of the child based on behavior in the preceding two months. Scores are expressed on a standard normal distribution with mean 50 and standard deviation 10. Z scores were created for analysis. A Z-score represents the distance from the population mean in terms of the number of standard deviations. The change in Z-score from Baseline to Year 1 was calculated for each patient. A positive number indicates an increase in the behavior, a negative number indicates a decrease in the behavior, and a zero indicates no change.
Time frame: Baseline to Year 1
Population: Evaluations done outside the age ranges specified for the assessments were excluded, the majority being assessments that were done on patients who were not yet 1.5 years of age.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Child Behavior Checklist (CBCL) Z-score Total Problems From Baseline to Year 1 | -0.3 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in Child Behavior Checklist (CBCL) Z-score Total Problems From Baseline to Year 1 | 0.1 units on a scale |
p-value: 0.131Wilcoxon (Mann-Whitney)
Secondary
Change in Cognitive Z-Score From Baseline to Year 1
Because patients in this study were evaluated with different cognitive assessments based on their age at the time of assessment (The Bayley-III Cognitive Composite, the WPSSI-III Full Scale IQ, and the WISC-IV Full Scale IQ Composite), with some patients being assessed using different tools at subsequent visits during the trial, a method for combining the assessments was employed to evaluate change in cognitive function over time in as many patients as possible. A cognitive Z-score was calculated for each participant at Baseline and Year 1 by adjusting each score by the relevant assessments' population mean and standard deviation. The Z-scores represent the distance from the population mean, as measured by standard deviations. The analysis presented here summarizes the change in Z-score between Baseline and Year 1. A positive number indicates an increase in cognitive function, a negative number indicates a decrease, and zero indicates no change.
Time frame: Baseline to Year 1
Population: When using all available cognitive assessments, the change in cognitive Z-score was available for 42 of the 63 participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Cognitive Z-Score From Baseline to Year 1 | 0.2 Z scores | Standard Error 0.2 |
| Placebo First, Then Autologous UCB Reinfusion | Change in Cognitive Z-Score From Baseline to Year 1 | 0.3 Z scores | Standard Error 0.2 |
p-value: 0.697t-test, 2 sided
Secondary
Change in CP-QOL Score
Children age four years or older at study entry were assessed using the disease-specific CP-QOL Child assessment tool as completed by a parent. The CP-QOL Child primary-caregiver proxy form is designed for children 4 - 12 with cerebral palsy and contains 66 items which assess physical, emotional, and social well being as well as access to services and acceptance by others. Scores are summarized in seven topic areas. Scores in each area range from 0 (worst health) to 100 (best health). The change score from Baseline to Year 1 is summarized here for each item. Negative scores indicated a decrease in quality of life, positive scores indicate an increase and zero indicates no change.
Time frame: Baseline, Year 1
Population: The analysis includes patients whose parents reported scores on each item at both Baseline and Year 1 and whose children met the age criteria for the questionnaire at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in CP-QOL Score | Family Health | -3.5 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in CP-QOL Score | Pain and impact of disability | 7 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in CP-QOL Score | Emotional well being and self esteem | -8.5 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in CP-QOL Score | Participation and physical health | -3 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in CP-QOL Score | Functioning | -11.5 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in CP-QOL Score | Social wellbeing and acceptance | -4 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in CP-QOL Score | Access to services | -13 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in CP-QOL Score | Social wellbeing and acceptance | 3 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in CP-QOL Score | Access to services | 15 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in CP-QOL Score | Emotional well being and self esteem | 10 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in CP-QOL Score | Family Health | 0 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in CP-QOL Score | Functioning | 3 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in CP-QOL Score | Pain and impact of disability | -5 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in CP-QOL Score | Participation and physical health | 17 units on a scale |
Comparison: H0: The 12 month Access to Services change score is identically distributed in patients assigned Autologous Cord Blood Reinfusion First and Placebo First.p-value: 0.055Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month 2 Emotional Well Being and Self Esteem change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.121Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month 2 Family Health change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.647Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Functioning change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.17Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Pain and Impact of Disability change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.41Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Participation and Physical Health change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.2Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Social wellbeing and acceptance change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.225Wilcoxon (Mann-Whitney)
Secondary
Change in Difficult Child Score From Baseline to Year 1
Parent stress was evaluated with the Parenting Stress Index - Short Form for children aged 0-12 years, which measures stress in three domains: Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child. Results in each domain are expressed as percentiles. Scores from the 15th-80th percentile are considered to be within the normal range. Scores at or above the 85th percentile considered high distress. Scores greater than the 89th percentile indicate clinically significant levels of distress. Analysis focused on changes in percentile scores between Baseline and Year 1. Positive numbers represent an increase in distress, negative numbers represent a decrease in distress, and zero indicates no change.
Time frame: Baseline to Year 1
Population: No participants were outside the age range for this test but change scores could not be calculated for some participants due either to missing data at the Baseline or Year 1 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Difficult Child Score From Baseline to Year 1 | -0.2 units on a scale | Standard Error 4.8 |
| Placebo First, Then Autologous UCB Reinfusion | Change in Difficult Child Score From Baseline to Year 1 | 6.9 units on a scale | Standard Error 5 |
p-value: 0.31t-test, 2 sided
Secondary
Change in IT-QOL Questionnaire Score
The Infant and Toddler Quality of Life Questionnaire (IT-QOL) was utilized for children ages one to three years at study entry.This 97-item questionnaire is completed by the parents and covers 12 concepts related to the physical, mental, and social well being of the child and the impact of their illness on the family. Scores range from 0 (worst health) to 100 (best health). The change from Baseline to Year 1 is summarized here for each of the 12 items on the questionnaire. Negative values indicate a decline in quality of life over time, positive values indicate an improvement, and zero indicates no change.
Time frame: Baseline to Year 1
Population: The analysis includes patients whose parents reported scores on each item at both Baseline and Year 1 and whose children met the age criteria for the questionnaire at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | Behavior | 4.5 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | Bodily Pain/Discomfort | 0 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | Family Cohesion | 0 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | General Behavior | 4 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | General Health Perceptions | 0 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | Global Behavior | 0 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | Growth and Development | 7.5 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | Overall Health | 0 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | Parental Impact-Emotional | 18 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | Physical Abilities | 5.50 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | Parental Impact-Time | 2 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Change in IT-QOL Questionnaire Score | Temperament and Moods | 4 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | Physical Abilities | 6 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | Behavior | 3 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | Growth and Development | 3 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | Bodily Pain/Discomfort | 8 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | Temperament and Moods | 2 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | Family Cohesion | 0 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | Overall Health | 0 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | General Behavior | 2 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | Parental Impact-Time | 0 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | General Health Perceptions | 0 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | Parental Impact-Emotional | 0 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in IT-QOL Questionnaire Score | Global Behavior | 0 units on a scale |
Comparison: H0: The 12-month Behavior change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.473Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Bodily Pain/Discomfort change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.377Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Family Cohesion change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.844Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month General Behavior change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.322Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month General Health Perceptions change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.927Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Global Behavior change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.199Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Growth and Development change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.294Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Overall Health change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.726Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Parental Impact-Emotional change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.315Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Parental Impact-Time change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.396Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Physical Abilities change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.381Wilcoxon (Mann-Whitney)
Comparison: H0: The 12-month Temperament and Moods change score is identically distributed in patients assigned Autologous UCB Reinfusion First and Placebo First.p-value: 0.869Wilcoxon (Mann-Whitney)
Secondary
Change in Loes Score of Functional MRI From Baseline to Year 1 and From Year 1 to Year 2
No data were collected from this procedure because enrolled subjects who were eligible to receive fMRI were unable to comply with the procedure.
Time frame: Baseline, Year 1, Year 2
Population: No data was available.
Secondary
Change in Parental Distress From Baseline to Year 1
Parent stress was evaluated with the Parenting Stress Index - Short Form for children aged 0-12 years, which measures stress in three domains: Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child. Results in each domain are expressed as percentiles. Scores from the 15th-80th percentile are considered to be within the normal range. Scores at or above the 85th percentile considered high distress. Scores greater than the 89th percentile indicate clinically significant levels of distress. Analysis focused on changes in percentile scores between Baseline and Year 1. Positive numbers represent an increase in distress, negative numbers represent a decrease in distress, and zero indicates no change.
Time frame: Baseline to Year 1
Population: No participants were outside the age range for this test but change scores could not be calculated for some participants due either to missing data at the Baseline or Year 1 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Parental Distress From Baseline to Year 1 | 1.0 Change in percentile score | Standard Error 4.5 |
| Placebo First, Then Autologous UCB Reinfusion | Change in Parental Distress From Baseline to Year 1 | -3.6 Change in percentile score | Standard Error 4.6 |
p-value: 0.478t-test, 2 sided
Secondary
Change in Parent-Child Dysfunctional Interaction From Baseline to Year 1
Parent stress was evaluated with the Parenting Stress Index - Short Form for children aged 0-12 years, which measures stress in three domains: Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child. Results in each domain are expressed as percentiles. Scores from the 15th-80th percentile are considered to be within the normal range. Scores at or above the 85th percentile considered high distress. Scores greater than the 89th percentile indicate clinically significant levels of distress. Analysis focused on changes in percentile scores between Baseline and Year 1. Positive numbers represent an increase in distress, negative numbers represent a decrease in distress, and zero indicates no change.
Time frame: Baseline to Year 1
Population: No participants were outside the age range for this test but change scores could not be calculated for some participants due either to missing data at the Baseline or Year 1 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Parent-Child Dysfunctional Interaction From Baseline to Year 1 | 0.0 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in Parent-Child Dysfunctional Interaction From Baseline to Year 1 | -10.0 units on a scale |
p-value: 0.029Wilcoxon (Mann-Whitney)
Secondary
Change in Peabody Gross Motor Quotient From Baseline to Year 1
The Peabody Developmental Motor Scales - Second Edition (PDMS-2) measures gross and fine motor skills in children from birth through five years of age. The Gross Motor Quotient score from the PDMS-2 was used in this study to evaluate gross motor function. The Gross Motor Quotient measures the ability to use large muscle systems for locomotion, maintain a stable posture when not moving, and throw/catch objects. The range of possible scores is 41 to 164. High scores indicate better gross motor function. Lower scores indicate less gross motor function ability. The change in Gross Motor Quotient from Baseline to Year 1 was evaluated in this study. Positive numbers indicate an increase in gross motor ability, negative numbers indicate decreases in gross motor function, and a zero indicates no change.
Time frame: Baseline to Year 1
Population: Participants outside of the applicable age range for the PDMS-2 at Baseline or Year 1 were excluded from the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Peabody Gross Motor Quotient From Baseline to Year 1 | 1 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in Peabody Gross Motor Quotient From Baseline to Year 1 | -0.5 units on a scale |
p-value: 0.39Wilcoxon (Mann-Whitney)
Secondary
Change in Pediatric Evaluation of Disability (PEDI) Mobility Score
The Pediatric Evaluation of Disability is used to evaluate functional skills in children aged 6 months to 7 years in three areas: Self Care, Mobility, and Social Function. The score in each area can range from 10-90. Higher scores indicate higher function. The change from Baseline to Year 1 in the Mobility score is presented here. Positive scores indicate increased function, negative scores indicate a decrease, and zero indicates no change.
Time frame: Baseline to Year 1
Population: Patients were excluded if change scores were not observable due to missing data at Baseline or Year 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Pediatric Evaluation of Disability (PEDI) Mobility Score | 0 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in Pediatric Evaluation of Disability (PEDI) Mobility Score | 0 units on a scale |
p-value: 0.76Wilcoxon (Mann-Whitney)
Secondary
Change in Pediatric Evaluation of Disability (PEDI) Self Care Score
The Pediatric Evaluation of Disability is used to evaluate functional skills in children aged 6 months to 7 years in three areas: Self Care, Mobility, and Social Function. The score in each area can range from 10-90. Higher scores indicate higher function. The change from Baseline to Year 1 in the Self Care score is presented here. Positive scores indicate increased function, negative scores indicate a decrease, and zero indicates no change.
Time frame: Baseline to Year 1
Population: Patients were excluded if change scores were not observable due to missing data at Baseline or Year 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Pediatric Evaluation of Disability (PEDI) Self Care Score | -3.7 units on a scale | Standard Error 2 |
| Placebo First, Then Autologous UCB Reinfusion | Change in Pediatric Evaluation of Disability (PEDI) Self Care Score | -2.2 units on a scale | Standard Error 1.4 |
p-value: 0.544t-test, 2 sided
Secondary
Change in Pediatric Evaluation of Disability (PEDI) Social Function Score
The Pediatric Evaluation of Disability is used to evaluate functional skills in children aged 6 months to 7 years in three areas: Self Care, Mobility, and Social Function. The score in each area can range from 10-90. Higher scores indicate higher function. The change from Baseline to Year 1 in the Social Function score is presented here. Positive scores indicate increased function, negative scores indicate a decrease, and zero indicates no change.
Time frame: Baseline to Year 1
Population: Patients were excluded if change scores were not observable due to missing data at Baseline or Year 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Pediatric Evaluation of Disability (PEDI) Social Function Score | -0.5 units on a scale | Standard Error 2 |
| Placebo First, Then Autologous UCB Reinfusion | Change in Pediatric Evaluation of Disability (PEDI) Social Function Score | -1.3 units on a scale | Standard Error 1.8 |
p-value: 0.76t-test, 2 sided
Secondary
Change in the Wechsler Intelligence Scale for Children (WISC-IV) From Baseline to Year 1.
Cognitive function was assessed in English-speaking study participants using one of three different tools depending on the age of the patient at the time of assessment: The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Wechsler Intelligence Scale for Children (WISC-IV), and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Some patients were assessed with different tools at subsequent visits as they aged during the conduct of the trial. The WISC-IV is designed for children 6 years 0 months to 16 years 11 months. This study used the Full Scale IQ, which ranges from 45 to 155 with a mean of 100 and standard deviation of 15. Higher scores indicate stronger cognitive function. Scores between 90 and 110 are considered to be within the range of average IQ.
Time frame: Baseline to Year 1
Population: Only one patient in this trial was evaluated with the WISC-IV and thus change over time could not be evaluated using this outcome measure. The single value for this patient is reported here.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo First, Then Autologous UCB Reinfusion | Change in the Wechsler Intelligence Scale for Children (WISC-IV) From Baseline to Year 1. | 103 Full Scale IQ Points |
Secondary
Change in Wechsler Preschool and Primary Scale of Intelligence (WPPSI) III Full Scale Intelligence Quotient (IQ) for Younger Children (Ages 2 Years & 6 Months to 3 Years & 11 Months) From Baseline to Year 1.
Cognitive function was assessed in English-speaking study participants using one of three different tools depending on the age of the patient at the time of assessment: The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Wechsler Intelligence Scale for Children (WISC-IV), and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Some patients were assessed with different tools at subsequent visits as they aged during the conduct of the trial. There are two versions of the WPPSI-III for two different age ranges: 2 years & 6 months to 3 years & 11 months, and 4 years to 7 years & 3 months. The Full Scale IQ is calculated for both age ranges and provides a continuous score with an average of 100 and a standard deviation of 15. Change from Baseline to Year 1 was evaluated, with positive numbers indicating an increase in cognitive ability, negative numbers indicating a decrease in cognitive ability, and zero indicating no change.
Time frame: Baseline to Year 1
Population: Change scores were evaluable in only 2 subjects who were assessed with the WPPSI-III at both Baseline and Year 1. One subject was randomized to Autologous Cord Blood and the other to Placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Wechsler Preschool and Primary Scale of Intelligence (WPPSI) III Full Scale Intelligence Quotient (IQ) for Younger Children (Ages 2 Years & 6 Months to 3 Years & 11 Months) From Baseline to Year 1. | 14 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in Wechsler Preschool and Primary Scale of Intelligence (WPPSI) III Full Scale Intelligence Quotient (IQ) for Younger Children (Ages 2 Years & 6 Months to 3 Years & 11 Months) From Baseline to Year 1. | -8 units on a scale |
Secondary
Change in Whole Brain Connectivity Measured by Diffusion Tensor Magnetic Resonance Imaging (MRI)
Change in number of connections in the brain as measured by diffusion tensor magnetic resonance imaging (MRI). Changes in connectivity are normalized to white matter volume of the brain. A positive number indicates an increase in connections, a negative number indicates a decrease, and zero indicates no change. The number of connections is expressed in terms of 10e5. For example, a change of 1 indicates an increase of 1x10e5 or 100,000 connections.
Time frame: Baseline to Year 1
Population: Patients without substantial morphologic brain abnormalities that prevented accurate anatomical image parcellation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Whole Brain Connectivity Measured by Diffusion Tensor Magnetic Resonance Imaging (MRI) | 0.3 Number of connections x10e5 |
| Placebo First, Then Autologous UCB Reinfusion | Change in Whole Brain Connectivity Measured by Diffusion Tensor Magnetic Resonance Imaging (MRI) | 0.2 Number of connections x10e5 |
Secondary
Correlation Between Clinical Response and RNA Expression of Neural, Endothelial and Inflammatory Cytokines Measured by RNA Arrays in Cord Blood Cells Given to These Patients.
Various pre-selected neural, angiogenic, and anti-inflammatory markers expressed by UCB cells and clinical response will be evaluated.
Time frame: 2 years
Secondary
Modified Ashworth Scale at Baseline
The Modified Ashworth Scale uses a 6 point scale (range 0, 1, 1+, 2, 3, or 4) to measure spasticity in 5 body regions (central, right upper extremity, left upper extremity, right lower extremity, and left lower extremity). Scores of 0 indicate no increase in muscle tone whereas a score of 4 indicates rigidity in flexion or extension.
Time frame: Baseline
Population: Patients are classified by their maximum score, regardless of body region.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Baseline | 0 @ Baseline | 2 Participants |
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Baseline | 1 @ Baseline | 4 Participants |
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Baseline | 1+ @ Baseline | 5 Participants |
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Baseline | 2 @ Baseline | 11 Participants |
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Baseline | 3 @ Baseline | 8 Participants |
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Baseline | 5 @ Baseline | 0 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Baseline | 3 @ Baseline | 8 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Baseline | 0 @ Baseline | 3 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Baseline | 2 @ Baseline | 11 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Baseline | 1 @ Baseline | 3 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Baseline | 5 @ Baseline | 2 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Baseline | 1+ @ Baseline | 3 Participants |
Secondary
Modified Ashworth Scale at Year 1
The Modified Ashworth Scale uses a 6 point scale (range 0, 1, 1+, 2, 3, or 4) to measure spasticity in 5 body regions (central, right upper extremity, left upper extremity, right lower extremity, and left lower extremity). Scores of 0 indicate no increase in muscle tone whereas a score of 4 indicates rigidity in flexion or extension.
Time frame: Year 1
Population: Patients are classified by their maximum score, regardless of body region.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Year 1 | 0 @ Year 1 | 1 Participants |
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Year 1 | 1 @ Year 1 | 3 Participants |
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Year 1 | 1+ @ Year 1 | 6 Participants |
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Year 1 | 2 @ Year 1 | 10 Participants |
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Year 1 | 3 @ Year 1 | 10 Participants |
| Autologous UCB Reinfusion First, Then Placebo | Modified Ashworth Scale at Year 1 | 4 @ Year 1 | 1 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Year 1 | 3 @ Year 1 | 6 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Year 1 | 0 @ Year 1 | 1 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Year 1 | 2 @ Year 1 | 9 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Year 1 | 1 @ Year 1 | 5 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Year 1 | 4 @ Year 1 | 1 Participants |
| Placebo First, Then Autologous UCB Reinfusion | Modified Ashworth Scale at Year 1 | 1+ @ Year 1 | 8 Participants |
Comparison: H0: The population distribution of Modified Ashworth Scale scores is the same at 1-year post-infusion with autologous cord blood and placebo.p-value: 0.233Wilcoxon (Mann-Whitney)
Secondary
Parent Experience of Child Illness (PECI)
The PECI is a 25-item measure designed to examine parental adjustment related to caring for a chronically ill child.
Time frame: Baseline to Year 1
Population: Data not collected due to the measure not being validated for children with Cerebral Palsy.
Other Pre-specified
Change in Barry-Albright Dystonia Total Score From Baseline to Year 1
The Barry-Albright Dystonia Scale measures generalized dystonia in eight body regions (eyes, mouth, neck, trunk, and the four extremities) using an ordinal scale (0=no dystonia, 1=slight dystonia, 2=mild dystonia, 3=moderate dystonia, and 4=severe dystonia). Individual scores for each region are summed to obtain a total score. The total score can range from 0 to 32 and higher scores indicate an overall greater degree of dystonia. The change in Barry-Albright Dystonia Total Score was evaluated from Baseline to Year 1. Positive numbers indicate increasing dystonia, negative numbers indicate a decrease in dystonia, and zero indicates no change.
Time frame: Baseline to Year 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Barry-Albright Dystonia Total Score From Baseline to Year 1 | 0.0 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Change in Barry-Albright Dystonia Total Score From Baseline to Year 1 | 0.0 units on a scale |
p-value: 0.762Wilcoxon (Mann-Whitney)
Post Hoc
Change in Whole Brain Connectivity Measured by Diffusion Tensor Magnetic Resonance Imaging (MRI) of All Subjects 1 Year Post-infusion With Autologous UCB
Change in whole brain connectivity measured by diffusion tensor magnetic resonance imaging (MRI). Changes in connectivity are normalized to white matter volume.
Time frame: 1 year post-infusion with autologous umbilical cord blood
Population: This group combines patients who received Autologous Umbilical Cord Blood whether at baseline or 1 year post-infusion with Placebo and is limited to patients without morphologic brain abnormalities that prevented accurate anatomical image parcellation. Low/High dose is defined as the median dose infused in all 63 enrolled patients, 2x10e7 TNCC/kg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Change in Whole Brain Connectivity Measured by Diffusion Tensor Magnetic Resonance Imaging (MRI) of All Subjects 1 Year Post-infusion With Autologous UCB | Low Infused Dose | 0.10 Number of connections x10e5 | Standard Deviation 0.32 |
| Autologous UCB Reinfusion First, Then Placebo | Change in Whole Brain Connectivity Measured by Diffusion Tensor Magnetic Resonance Imaging (MRI) of All Subjects 1 Year Post-infusion With Autologous UCB | High Infused Dose | 0.30 Number of connections x10e5 | Standard Deviation 0.24 |
Comparison: H0: The true mean 1-year change in normalized whole brain connectivity is the same in patients infused with Low and High doses of autologous umbilical cord blood.p-value: 0.0495% CI: [0.01, 0.38]Wilcoxon (Mann-Whitney)
Post Hoc
Gross Motor Function Measure 66 (GMFM-66) Change Score at 1 Year by Infused Dose
Gross Motor Function Measure 66 (GMFM-66) Change Score at 1 Year. Analyzed by infused dose, above or below the median. The GMFM-66 is a clinical tool used to evaluate gross motor function in children with cerebral palsy and is scored using a propriety software program called the Gross Motor Ability Estimator (GMAE) that produces an interval level continuous score ranging from 0 to 100. Higher scores indicate better motor function. A negative change in GMFM-66 score indicates a reduction in motor function, a positive change indicates improvement in motor function, and zero indicates no change in motor function.
Time frame: 1 Year
Population: Patients randomized to Autologous Umbilical Cord Blood were divided into two groups for this analysis: Low and High dose. The median dose infused in these 32 patients was used as the cut point to define Low and High doses: 1.98x10e7 total nucleated cells per kilogram of patient weight (TNCC/kg).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Gross Motor Function Measure 66 (GMFM-66) Change Score at 1 Year by Infused Dose | All | 6.5 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Gross Motor Function Measure 66 (GMFM-66) Change Score at 1 Year by Infused Dose | Low Infused Dose | 4 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Gross Motor Function Measure 66 (GMFM-66) Change Score at 1 Year by Infused Dose | High Infused Dose | 8.5 units on a scale |
| Placebo First, Then Autologous UCB Reinfusion | Gross Motor Function Measure 66 (GMFM-66) Change Score at 1 Year by Infused Dose | All | 6.0 units on a scale |
Comparison: H0: The population distribution of the 1-year GMFM-66 change score is the same for patients infused with Low and High doses of autologous umbilical cord blood.p-value: 0.05Wilcoxon (Mann-Whitney)
Comparison: H0: The population distribution of the 1-year GMFM-66 change score is the same for patients infused with High doses of autologous umbilical cord blood and Placebo.p-value: 0.15Wilcoxon (Mann-Whitney)
Comparison: H0: The population distribution of the 1-year GMFM-66 change score is the same for patients infused with Low doses of autologous umbilical cord blood and placebo.p-value: 0.21Wilcoxon (Mann-Whitney)
Post Hoc
Observed Minus Expected GMFM-66 Change Score of All Subjects Receiving Autologous UCB and Who Are Greater Than or Equal to 2 Years of Age
Validated functional curves were used to identify the expected 1-year change in GMFM-66 score given each child's age and Gross Motor Function Classification System (GMFCS) Level at baseline. The difference between observed change (in this study) and expected change was then calculated for each participant. The threshold defining Low/High dose is the median dose infused in all 63 enrolled patients, 2x10e7 TNCC/kg.
Time frame: 1 year post-infusion with autologous umbilical cord blood
Population: Patients who received cord blood at baseline and 1 year post-infusion with Placebo, and who are \>=2 years old (to allow calculation of expected GMFM-66 change scores from published data). An additional 6 are excluded because change scores were not observable due to subject withdrawal (5) or inability to comply due to a broken leg (1).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Observed Minus Expected GMFM-66 Change Score of All Subjects Receiving Autologous UCB and Who Are Greater Than or Equal to 2 Years of Age | All | 1.1 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Observed Minus Expected GMFM-66 Change Score of All Subjects Receiving Autologous UCB and Who Are Greater Than or Equal to 2 Years of Age | Low Infused Dose | -1.1 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Observed Minus Expected GMFM-66 Change Score of All Subjects Receiving Autologous UCB and Who Are Greater Than or Equal to 2 Years of Age | High Infused Dose | 3.6 units on a scale |
Comparison: H0: The population distribution of differences between observed and expected GMFM-66 change scores at 1-year post-infusion is the same for patients receiving Low and High doses of autologous umbilical cord blood.p-value: <0.01Wilcoxon (Mann-Whitney)
Post Hoc
Peabody Gross Motor Quotient Change Score 1 Year After Receiving Autologous UCB.
The Peabody Developmental Motor Scales - Second Edition (PDMS-2), Gross Motor Quotient change score was calculated for each patient at 1 year after infusion with autologous umbilical cord blood. Analyzed by infused dose, above or below the median. The Gross Motor Quotient score from the PDMS-2 was used in this study to evaluate gross motor function. The Gross Motor Quotient measures the ability to use large muscle systems for locomotion, maintain a stable posture when not moving, and throw/catch objects. The range of possible scores is 41 to 164. High scores indicate better gross motor function. Lower scores indicate less gross motor function ability.
Time frame: 1 year post-infusion with autologous umbilical cord blood
Population: This group combines patients who received Autologous Umbilical Cord Blood at baseline or 1 year post-infusion with Placebo, and who are within the age range specified for the PDMS-2. The threshold defining Low/High dose is the median dose infused in all 63 enrolled patients, 2x10e7 TNCC/kg.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Autologous UCB Reinfusion First, Then Placebo | Peabody Gross Motor Quotient Change Score 1 Year After Receiving Autologous UCB. | Low Infused Dose | 0 units on a scale |
| Autologous UCB Reinfusion First, Then Placebo | Peabody Gross Motor Quotient Change Score 1 Year After Receiving Autologous UCB. | High Infused Dose | 3 units on a scale |
p-value: 0.03Wilcoxon (Mann-Whitney)