Trial Outcomes & Findings for A Randomized Study of Autologous Umbilical Cord Blood Reinfusion in Children With Cerebral Palsy (NCT NCT01147653)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

Baseline to Year 1

Results posted on

2023-01-04

Participant Flow

Participants were enrolled and randomized on the same day.

Participant milestones

Participant milestones
Measure	Autologous UCB Reinfusion First, Then Placebo Subjects receive autologous umbilical cord blood at Baseline, then Placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion Subjects receive Placebo at Baseline, then autologous umbilical cord blood at Year 1.
Year 1 STARTED	32	31
Year 1 COMPLETED	32	31
Year 1 NOT COMPLETED	0	0
Year 2 STARTED	32	31
Year 2 COMPLETED	30	28
Year 2 NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Autologous UCB Reinfusion First, Then Placebo Subjects receive autologous umbilical cord blood at Baseline, then Placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion Subjects receive Placebo at Baseline, then autologous umbilical cord blood at Year 1.
Year 2 Withdrawal by Subject	2	3

Baseline Characteristics

A Randomized Study of Autologous Umbilical Cord Blood Reinfusion in Children With Cerebral Palsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Autologous UCB First, Then Placebo n=32 Participants Subjects receive autologous umbilical cord blood at Baseline, then Placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=31 Participants Subjects receive Placebo at Baseline, then autologous umbilical cord blood at Year 1.	Total n=63 Participants Total of all reporting groups
Age, Continuous	2.1 Years n=5 Participants	2.3 Years n=7 Participants	2.3 Years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	27 Participants n=7 Participants	56 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	28 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
GMFCS Level Level I	11 Participants n=5 Participants	6 Participants n=7 Participants	17 Participants n=5 Participants
GMFCS Level Level II	9 Participants n=5 Participants	15 Participants n=7 Participants	24 Participants n=5 Participants
GMFCS Level Level III	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
GMFCS Level Level IV	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Type of Cerebral Palsy Spastic Diplegia	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Type of Cerebral Palsy Spastic Hemiplegia	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Type of Cerebral Palsy Spastic Quadriplegia	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Type of Cerebral Palsy Hypotonic Quadriplegia	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Year 1

Population: All enrolled patients were analyzed as randomized from 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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=32 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=31 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Gross Motor Function Measure 66 (GMFM-66) Score	7.5 units on a scale Standard Deviation 6.8	6.9 units on a scale Standard Deviation 5.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=24 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=26 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Peabody Gross Motor Quotient From Baseline to Year 1	1 units on a scale Interval -10.0 to 20.0	-0.5 units on a scale Interval -19.0 to 15.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=24 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=21 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in IT-QOL Questionnaire Score Overall Health	0 units on a scale Interval -30.0 to 30.0	0 units on a scale Interval -40.0 to 25.0
Change in IT-QOL Questionnaire Score Behavior	4.5 units on a scale Interval -13.0 to 20.0	3 units on a scale Interval -15.0 to 20.0
Change in IT-QOL Questionnaire Score Bodily Pain/Discomfort	0 units on a scale Interval -42.0 to 42.0	8 units on a scale Interval -25.0 to 25.0
Change in IT-QOL Questionnaire Score Family Cohesion	0 units on a scale Interval -40.0 to 40.0	0 units on a scale Interval -25.0 to 25.0
Change in IT-QOL Questionnaire Score General Behavior	4 units on a scale Interval -35.0 to 29.0	2 units on a scale Interval -21.0 to 28.0
Change in IT-QOL Questionnaire Score General Health Perceptions	0 units on a scale Interval -23.0 to 21.0	0 units on a scale Interval -19.0 to 25.0
Change in IT-QOL Questionnaire Score Global Behavior	0 units on a scale Interval -40.0 to 55.0	0 units on a scale Interval -55.0 to 30.0
Change in IT-QOL Questionnaire Score Growth and Development	7.5 units on a scale Interval -22.0 to 35.0	3 units on a scale Interval -28.0 to 30.0
Change in IT-QOL Questionnaire Score Parental Impact-Emotional	18 units on a scale Interval -14.0 to 50.0	0 units on a scale Interval -21.0 to 53.0
Change in IT-QOL Questionnaire Score Parental Impact-Time	2 units on a scale Interval -22.0 to 43.0	0 units on a scale Interval -43.0 to 47.0
Change in IT-QOL Questionnaire Score Physical Abilities	5.50 units on a scale Interval -15.0 to 35.0	6 units on a scale Interval -33.0 to 34.0
Change in IT-QOL Questionnaire Score Temperament and Moods	4 units on a scale Interval -20.0 to 25.0	2 units on a scale Interval -8.0 to 30.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=6 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=5 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in CP-QOL Score Participation and physical health	-3 units on a scale Interval -20.0 to 12.0	17 units on a scale Interval -20.0 to 35.0
Change in CP-QOL Score Access to services	-13 units on a scale Interval -32.0 to 12.0	15 units on a scale Interval -13.0 to 28.0
Change in CP-QOL Score Emotional well being and self esteem	-8.5 units on a scale Interval -30.0 to 4.0	10 units on a scale Interval -13.0 to 90.0
Change in CP-QOL Score Family Health	-3.5 units on a scale Interval -37.0 to 3.0	0 units on a scale Interval -18.0 to 19.0
Change in CP-QOL Score Functioning	-11.5 units on a scale Interval -22.0 to 6.0	3 units on a scale Interval -14.0 to 30.0
Change in CP-QOL Score Pain and impact of disability	7 units on a scale Interval -17.0 to 17.0	-5 units on a scale Interval -22.0 to 3.0
Change in CP-QOL Score Social wellbeing and acceptance	-4 units on a scale Interval -11.0 to 4.0	3 units on a scale Interval -17.0 to 12.0

SECONDARY outcome

Timeframe: Baseline to Year 1

Population: Patients without substantial morphologic brain abnormalities that prevented accurate anatomical image parcellation.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=23 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=15 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Whole Brain Connectivity Measured by Diffusion Tensor Magnetic Resonance Imaging (MRI)	0.3 Number of connections x10e5 Interval -0.5 to 0.6	0.2 Number of connections x10e5 Interval -0.5 to 0.6

SECONDARY outcome

Timeframe: Baseline, Year 1, Year 2

Population: No data was available.

No data were collected from this procedure because enrolled subjects who were eligible to receive fMRI were unable to comply with the procedure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=14 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=13 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
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 3.0	8.1 units on a scale Standard Error 3.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=1 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=1 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
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	-8 units on a scale

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=1 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in the Wechsler Intelligence Scale for Children (WISC-IV) From Baseline to Year 1.	—	103 Full Scale IQ Points

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=21 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=21 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Cognitive Z-Score From Baseline to Year 1	0.2 Z scores Standard Error 0.2	0.3 Z scores Standard Error 0.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=9 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=10 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Assisting Hand Assessment (AHA) Score From Baseline to Year 1	5.4 units on a scale Standard Error 2.1	5.1 units on a scale Standard Error 2.3

SECONDARY outcome

Timeframe: Baseline to Year 1

Population: Patients were excluded if change scores were not observable due to missing data at Baseline or 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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=31 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=29 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Pediatric Evaluation of Disability (PEDI) Self Care Score	-3.7 units on a scale Standard Error 2	-2.2 units on a scale Standard Error 1.4

SECONDARY outcome

Timeframe: Baseline to Year 1

Population: Patients were excluded if change scores were not observable due to missing data at Baseline or 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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=31 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=29 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Pediatric Evaluation of Disability (PEDI) Mobility Score	0 units on a scale Interval -21.81 to 19.8	0 units on a scale Interval -18.5 to 13.21

SECONDARY outcome

Timeframe: Baseline to Year 1

Population: Patients were excluded if change scores were not observable due to missing data at Baseline or 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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=31 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=29 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Pediatric Evaluation of Disability (PEDI) Social Function Score	-0.5 units on a scale Standard Error 2.0	-1.3 units on a scale Standard Error 1.8

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=23 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=22 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Child Behavior Checklist (CBCL) Z-score Internalizing Problems From Baseline to Year 1	-0.6 units on a scale Interval -1.8 to 2.5	0.0 units on a scale Interval -2.2 to 1.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=23 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=22 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
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	0.1 units on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=23 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=22 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Child Behavior Checklist (CBCL) Z-score Total Problems From Baseline to Year 1	-0.3 units on a scale Interval -2.0 to 2.8	0.1 units on a scale Interval -1.9 to 1.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=28 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=29 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Parental Distress From Baseline to Year 1	1.0 Change in percentile score Standard Error 4.5	-3.6 Change in percentile score Standard Error 4.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=28 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=29 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Parent-Child Dysfunctional Interaction From Baseline to Year 1	0.0 units on a scale Interval -35.0 to 45.0	-10.0 units on a scale Interval -56.0 to 41.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=28 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=29 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Difficult Child Score From Baseline to Year 1	-0.2 units on a scale Standard Error 4.8	6.9 units on a scale Standard Error 5.0

SECONDARY outcome

Timeframe: Baseline

Population: Patients are classified by their maximum score, regardless of body region.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=30 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=30 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Modified Ashworth Scale at Baseline 0 @ Baseline	2 Participants	3 Participants
Modified Ashworth Scale at Baseline 1 @ Baseline	4 Participants	3 Participants
Modified Ashworth Scale at Baseline 1+ @ Baseline	5 Participants	3 Participants
Modified Ashworth Scale at Baseline 2 @ Baseline	11 Participants	11 Participants
Modified Ashworth Scale at Baseline 3 @ Baseline	8 Participants	8 Participants
Modified Ashworth Scale at Baseline 5 @ Baseline	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Year 1

Population: Patients are classified by their maximum score, regardless of body region.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=31 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=30 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Modified Ashworth Scale at Year 1 1 @ Year 1	3 Participants	5 Participants
Modified Ashworth Scale at Year 1 0 @ Year 1	1 Participants	1 Participants
Modified Ashworth Scale at Year 1 1+ @ Year 1	6 Participants	8 Participants
Modified Ashworth Scale at Year 1 2 @ Year 1	10 Participants	9 Participants
Modified Ashworth Scale at Year 1 3 @ Year 1	10 Participants	6 Participants
Modified Ashworth Scale at Year 1 4 @ Year 1	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=1 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Bruininks-Oseretsky-2 Total Motor Composite From Baseline to Year 1	-1 units on a scale	—

SECONDARY outcome

Timeframe: 2 years

Various pre-selected neural, angiogenic, and anti-inflammatory markers expressed by UCB cells and clinical response will be evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Year 1

Population: Data not collected due to the measure not being validated for children with Cerebral Palsy.

The PECI is a 25-item measure designed to examine parental adjustment related to caring for a chronically ill child.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=32 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=31 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Change in Barry-Albright Dystonia Total Score From Baseline to Year 1	0.0 units on a scale Interval -12.0 to 10.0	0.0 units on a scale Interval -11.0 to 28.0

POST_HOC outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=32 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion n=31 Participants Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Gross Motor Function Measure 66 (GMFM-66) Change Score at 1 Year by Infused Dose All	6.5 units on a scale Interval -3.0 to 19.0	6.0 units on a scale Interval -5.0 to 19.0
Gross Motor Function Measure 66 (GMFM-66) Change Score at 1 Year by Infused Dose Low Infused Dose	4 units on a scale Interval -3.0 to 19.0	—
Gross Motor Function Measure 66 (GMFM-66) Change Score at 1 Year by Infused Dose High Infused Dose	8.5 units on a scale Interval 0.0 to 19.0	—

POST_HOC outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=46 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
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 Interval -8.1 to 15.4	—
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 Interval -8.1 to 12.9	—
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 Interval -5.6 to 15.4	—

POST_HOC outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=47 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
Peabody Gross Motor Quotient Change Score 1 Year After Receiving Autologous UCB. Low Infused Dose	0 units on a scale Interval -10.0 to 15.0	—
Peabody Gross Motor Quotient Change Score 1 Year After Receiving Autologous UCB. High Infused Dose	3 units on a scale Interval -8.0 to 20.0	—

POST_HOC outcome

Timeframe: 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.

Change in whole brain connectivity measured by diffusion tensor magnetic resonance imaging (MRI). Changes in connectivity are normalized to white matter volume.

Outcome measures

Outcome measures
Measure	Autologous UCB Reinfusion First, Then Placebo n=38 Participants Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.	Placebo First, Then Autologous UCB Reinfusion Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
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	—
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	—

Adverse Events

Autologous Umbilical Cord Blood Reinfusion

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Autologous Umbilical Cord Blood Reinfusion n=63 participants at risk All participants will be treated with autologous cord blood reinfusion, but the time course will vary between groups and participants will be blinded to the order in which they receive infusions. Autologous Umbilical Cord Blood or Placebo: All participants will be treated with autologous cord blood reinfusion, but the time course will vary between groups and participants will be blinded to the order in which they receive infusions. Patients will be randomized to receive their autologous umbilical cord blood cells first or placebo first. Subjects will receive both infusions but will be randomized and blinded by which they are receiving first and second.	Placebo n=63 participants at risk All participants will be treated with autologous cord blood reinfusion, but the time course will vary between groups and participants will be blinded to the order in which they receive infusions. Autologous Umbilical Cord Blood or Placebo: All participants will be treated with autologous cord blood reinfusion, but the time course will vary between groups and participants will be blinded to the order in which they receive infusions. Patients will be randomized to receive their autologous umbilical cord blood cells first or placebo first. Subjects will receive both infusions but will be randomized and blinded by which they are receiving first and second.
Endocrine disorders Flushed in face with hypersensitivity rash on trunk	0.00% 0/63 • 2 years Since there is no washout period for autologous umbilical cord blood transfusions, the only adverse events included in the placebo arm were those events that occurred in subjects that had not yet received cord blood. All other adverse events that occurred in subjects that had been exposed to cord blood at either Baseline or Year 1 were included in the "Autologous Umbilical Cord Blood" arm.	1.6% 1/63 • Number of events 1 • 2 years Since there is no washout period for autologous umbilical cord blood transfusions, the only adverse events included in the placebo arm were those events that occurred in subjects that had not yet received cord blood. All other adverse events that occurred in subjects that had been exposed to cord blood at either Baseline or Year 1 were included in the "Autologous Umbilical Cord Blood" arm.

Other adverse events

Additional Information

Jesse Troy, PhD

Duke University School of Medicine, Division of Pediatric Blood and Marrow Transplantation

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place