Allogenic Umbilical Cord Blood and Erythropoietin Combination Therapy for Cerebral Palsy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sung Kwang Medical Foundation
ClinicalTrials.gov Identifier:
NCT01193660
First received: August 29, 2010
Last updated: March 1, 2012
Last verified: March 2012
Results First Received: October 11, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Cerebral Palsy
Interventions: Biological: Umbilical Cord Blood Infusion
Drug: Erythropoietin Injection
Other: Active Rehabilitation
Other: Placebo Umbilical Cord Blood
Other: Placebo Erythropoietin

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Enrollment Period: May 31, 2010 through April 9, 2011 All participants were recruited at CHA Bundang Medical Center.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
We tried to recruit 106 subjects. Finally 105 patients were enrolled at the beginning of the overall study and none of the participants were washed out before assignment to groups.

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Participant Flow:   Overall Study
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
STARTED     35     36     34  
COMPLETED     31     33     32  
NOT COMPLETED     4     3     2  
Withdrawal by Subject                 2                 3                 1  
Death                 1                 0                 0  
Physician Decision                 1                 0                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation
Total Total of all reporting groups

Baseline Measures
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation     Total  
Number of Participants  
[units: participants]
  35     36     34     105  
Age  
[units: participants]
       
<=18 years     35     36     34     105  
Between 18 and 65 years     0     0     0     0  
>=65 years     0     0     0     0  
Age  
[units: months]
Mean ± Standard Deviation
  45.71  ± 18.91     50.05  ± 24.45     46.0  ± 19.58     47.30  ± 21.07  
Gender  
[units: participants]
       
Female     13     11     9     33  
Male     22     25     25     72  
Region of Enrollment  
[units: participants]
       
Korea, Republic of     35     36     34     105  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Changes in Motor Performance   [ Time Frame: Baseline -1 month - 3 months - 6 months ]

Measure Type Primary
Measure Title Changes in Motor Performance
Measure Description GMPM (Gross Motor Performance Measure) as a standardized measurement tool for assessing quality of movement regarding 3 properties of 5 ones; alignment, coordination, dissociated movement, stability, and weight shift (range: 0~100, Higher value means better motor quality). We reported changes of GMPM score between each assessment time points. Categories of outcome table are baseline and values of just subtracting the latter raw scores from the former ones.
Time Frame Baseline -1 month - 3 months - 6 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  31     33     32  
Changes in Motor Performance  
[units: units on a scale]
Mean ± Standard Error
     
Baseline     34.5  ± 2.7     38.2  ± 2.8     35.5  ± 2.9  
1 month - Baseline     7.00  ± 1.3     4.5  ± 0.6     6.0  ± 1.0  
3 months - Baseline     11.5  ± 1.5     7.5  ± 0.8     8.1  ± 1.2  
6 months - Baseline     14.5  ± 1.8     9.2  ± 0.8     9.6  ± 1.2  
3 months - 1 month     4.5  ± 0.7     2.9  ± 0.5     2.1  ± 0.6  
6 months - 1 month     7.5  ± 0.9     4.7  ± 0.7     3.6  ± 0.7  
6 months - 3 months     3.1  ± 0.6     1.7  ± 0.5     1.5  ± 0.4  


Statistical Analysis 1 for Changes in Motor Performance
Groups [1] All groups
Method [2] Repeated Measure ANOVA
P Value [3] <0.05
Wilks' Lambda (group*visit effect) [4] 2.59
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  In our analysis, the null hypothesis is that the effects of 3 experimental groups are same, and the alternative hypothesis is that the therapeutic effect of combination intervention Group (Umbilical Cord Blood + Erythropoietin + Rehabilitation) is higher than that of either Erythropoietin + Rehabilitation or Rehabilitation Group. This is a pilot study and power calculation was not applicable. The sample size of each group is over 30 and is considered to follow approximately normal distribution.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



2.  Primary:   Changes in Standardized Gross Motor Function   [ Time Frame: Baseline - 1 month - 3 months - 6 months ]

Measure Type Primary
Measure Title Changes in Standardized Gross Motor Function
Measure Description GMFM (Gross Motor Function Measure) as a standardized measurement tool for assessing Gross Motor Function consisting of sub-scales; lying & rolling, sitting, crawling & kneeling, standing, walking, running & jumping (range: 0~100 , Higher value means better gross motor function). We reported changes of GMFM between each assessment time points. Categories of outcome table are baseline and values of just subtracting the latter raw scores from the former ones.
Time Frame Baseline - 1 month - 3 months - 6 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  31     33     32  
Changes in Standardized Gross Motor Function  
[units: units on a scale]
Mean ± Standard Error
     
Baseline     36.0  ± 4.7     42.6  ± 4.9     36.8  ± 4.5  
1 month - Baseline     3.7  ± 0.4     4.3  ± 0.5     4.6  ± 0.6  
3 months - Baseline     6.5  ± 0.9     6.8  ± 0.8     6.4  ± 0.7  
6 months - Baseline     9.1  ± 1.2     9.0  ± 1.1     7.8  ± 0.9  
3 months - 1 month     2.9  ± 0.8     2.5  ± 0.5     1.8  ± 0.4  
6 months - 1 month     5.4  ± 1.2     4.7  ± 0.9     3.1  ± 0.6  
6 months - 3 months     2.6  ± 0.5     2.2  ± 0.6     1.3  ± 0.4  


Statistical Analysis 1 for Changes in Standardized Gross Motor Function
Groups [1] All groups
Method [2] Repeated Measure ANOVA
P Value [3] <0.05
interaction of group and visit [4] 0.90
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  In our analysis, the null hypothesis is that the effects of 3 experimental groups are same, and the alternative hypothesis is that the therapeutic effect of combination intervention Group (Umbilical Cord Blood + Erythropoietin + Rehabilitation) is higher than that of either Erythropoietin + Rehabilitation or Rehabilitation Group. This is a pilot study and power calculation was not applicable. The sample size of each group is over 30 and is considered to follow approximately normal distribution.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Changes in Cognitive Neurodevelopmental Outcome   [ Time Frame: Baseline -1 month - 3 months - 6 months ]

Measure Type Secondary
Measure Title Changes in Cognitive Neurodevelopmental Outcome
Measure Description Korean version of Bayley Scale of Infant Development-II (K-BSID-II) Mental Scales (higher value means better mental function: 0 - worst, 178 - best). We reported changes of BSID-II Mental Scale raw score between each assessment time points. Categories of outcome data are values of subtracting the latter scores from the former ones.
Time Frame Baseline -1 month - 3 months - 6 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  31     33     32  
Changes in Cognitive Neurodevelopmental Outcome  
[units: units on a scale]
Mean ± Standard Error
     
BSID-II Mental Scale: Baseline     94.1  ± 9.1     105.9  ± 8.9     86.6  ± 9.0  
BSID-II Mental Scale: 1 month - Baseline     8.2  ± 1.3     3.4  ± 0.5     3.3  ± 0.6  
BSID-II Mental Scale: 3 months - Baseline     12.0  ± 1.4     7.4  ± 0.9     5.8  ± 0.8  
BSID-II Mental Scale: 6 months - Baseline     17.6  ± 1.8     11.5  ± 1.3     9.9  ± 1.6  
BSID-II Mental Scale: 3 months - 1 month     3.8  ± 0.8     4.0  ± 0.7     2.5  ± 0.7  
BSID-II Mental Scale: 6 months - 1 month     9.4  ± 1.4     8.1  ± 1.3     6.6  ± 1.4  
BSID-II Mental Scale: 6 months - 3 months     5.6  ± 1.2     4.1  ± 0.8     4.1  ± 1.0  


Statistical Analysis 1 for Changes in Cognitive Neurodevelopmental Outcome
Groups [1] All groups
Method [2] Repeated Measure ANOVA
P Value [3] <0.05
Wilks' Lambda (group*visit effect) [4] 3.94
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The null hypothesis is that in terms of K-BSID-II MENTAL Scale, the effects of 3 groups are same, and the alternative one is that the therapeutic effect of combination intervention Group (Umbilical Cord Blood + Erythropoietin + Rehabilitation) is higher than that of either Erythropoietin + Rehabilitation or Rehabilitation Group. This is a pilot study and power calculation was not applicable. The sample size of each group is over 30 and is considered to follow approximately normal distribution.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Changes in Motor Neurodevelopmental Outcome   [ Time Frame: Baseline - 1 month - 3 months - 6 months ]

Measure Type Secondary
Measure Title Changes in Motor Neurodevelopmental Outcome
Measure Description Korean version of Bayley Scale of Infant Development-II (K-BSID-II) Motor Scales (higher value means better motor function: 0 - worst, 111 - best). We reported changes of BSID-II Motor Scale raw score between each assessment time points. Categories of outcome data are values of subtracting the latter scores from the former ones.
Time Frame Baseline - 1 month - 3 months - 6 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  31     33     32  
Changes in Motor Neurodevelopmental Outcome  
[units: units on a scale]
Mean ± Standard Error
     
BSID-II Motor Scale: Baseline     45.2  ± 4.7     53.3  ± 5.0     45.5  ± 4.6  
BSID-II Motor Scale: 1 month - Baseline     5.0  ± 1.5     5.2  ± 2.1     2.7  ± 0.6  
BSID-II Motor Scale: 3 months - Baseline     9.5  ± 1.9     6.8  ± 2.1     4.3  ± 0.8  
BSID-II Motor Scale: 6 months - Baseline     11.7  ± 2.0     7.6  ± 2.2     5.2  ± 0.9  
BSID-II Motor Scale: 3 months - 1 month     4.5  ± 1.0     1.6  ± 0.5     1.5  ± 0.4  
BSID-II Motor Scale: 6 months - 1 month     6.7  ± 1.3     2.5  ± 0.6     2.5  ± 0.5  
BSID-II Motor Scale: 6 months - 3 months     2.2  ± 0.6     0.9  ± 0.4     1.0  ± 0.4  


Statistical Analysis 1 for Changes in Motor Neurodevelopmental Outcome
Groups [1] All groups
Method [2] Repeated Measure ANOVA
P Value [3] <0.05
Wilks' Lambda (group*visit effect) [4] 2.70
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The null hypothesis is that in terms of K-BSID-II MOTOR Scale, the effects of 3 groups are same, and the alternative one is that the therapeutic effect of combination intervention Group (Umbilical Cord Blood + Erythropoietin + Rehabilitation) is higher than that of either Erythropoietin + Rehabilitation or Rehabilitation Group. This is a pilot study and power calculation was not applicable. The sample size of each group is over 30 and is considered to follow approximately normal distribution.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



5.  Secondary:   Changes in Brain MRI   [ Time Frame: Baseline - 6 months ]

Measure Type Secondary
Measure Title Changes in Brain MRI
Measure Description Changes on brain Diffusion Tensor Image (DTI); DTI provides quantitative information about the microscopic integrity of white matter. White matter normally possesses a high degree of diffusion anisotropy than gray matter. We can measure fractional anisotropy (FA) value in DTI imaging and it ranges from 0 to 1. Higher FA value of a certain region of interest means the area has more integrity of white matter.
Time Frame Baseline - 6 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  30     31     29  
Changes in Brain MRI  
[units: units on a scale]
Mean ± Standard Error
     
Anterior portion of Rt. posterior Internal Capsule     0.03  ± 0.01     0.01  ± 0.01     0.01  ± 0.01  
Posterior portion of Rt posterior Internal Capsule     0.04  ± 0.01     0.02  ± 0.01     0.02  ± 0.02  
Anterior portion of Lt. posterior Internal Capsule     0.03  ± 0.01     0.02  ± 0.01     0.04  ± 0.02  
Posterior portion of Lt posterior Internal Capsule     0.05  ± 0.02     0.04  ± 0.02     0.05  ± 0.02  

No statistical analysis provided for Changes in Brain MRI



6.  Secondary:   Comparison of Changes in Brain Glucose Metabolism Using by Brain 18F-FDG PET: Increased and Decreased Areas of Brain Glucose Metabolism   [ Time Frame: Baseline - 2 weeks ]

Measure Type Secondary
Measure Title Comparison of Changes in Brain Glucose Metabolism Using by Brain 18F-FDG PET: Increased and Decreased Areas of Brain Glucose Metabolism
Measure Description 18F-FDG PET imaging was performed twice prior to and then 2 weeks post-treatment. Ninety slices of each emission image were obtained, and all scans were reviewed by a nuclear physician. Spatial pre-processing and statistical analyses were performed using SPM8 implanted in Matlab to compare differences in regional brain glucose metabolism between groups and differences between pre- and post-therapy imaging data. We reported increased areas and decreased areas of glucose metabolism in three groups. We defined that "1" refers to INCREASED areas, "-1", DECREASED areas and "0", just NO CHANGE.
Time Frame Baseline - 2 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  31     33     32  
Comparison of Changes in Brain Glucose Metabolism Using by Brain 18F-FDG PET: Increased and Decreased Areas of Brain Glucose Metabolism  
[units: units on a scale]
     
Rt. Lentiform Nucleus, Gray Matter, Putamen     1     0     0  
Lt. Frontal Lobe, Medial Frontal Gyrus     1     0     0  
Lt. Sub-lobar, Insula     1     0     0  
Lt. Lentiform Nucleus, Gray Matter, Putamen     1     0     0  
Lt.Lentiform Nucleus, Gray Matter, Globus Pallidus     1     0     0  
Lt. Midbrain (Thalamus)     1     0     0  
Rt. Parietal Lobe, Precuneus     1     0     0  
Lt. Temporal Lobe, Middle Temporal Gyrus     1     0     0  
Rt. Parietal Lobe, Pre- and Post-central Gyrus     1     0     0  
Rt. Frontal Lobe, Paracentral Lobule     0     1     0  
Rt. Limbic Lobe, Anterior Cingulate     0     1     0  
Lt. Frontal Lobe, Precentral Gyrus     0     1     0  
Lt. Lentiform Nucleus, Putamen     0     1     0  
Rt. Cerebellar Anterior Lobe, Culmen     0     1     1  
Lt. Cerebellar Posterior Lobe, Cerebellar Tonsil     0     1     1  
Rt. Frontal Lobe, Orbital Gyrus     0     1     1  
Rt. Occipital Lobe, Middle Occipital Gyrus     -1     0     0  
Lt. Limbic Lobe, Parahippocampal Gyrus     -1     0     0  
Rt. Limbic Lobe, Parahippocampal Gyrus     -1     0     0  
Rt Cerebellum, Posterior Lobe, Declive     0     -1     0  
Rt Cerebellum, Anterior Lobe, Culmen, Occipital     0     -1     0  
Lt Cerebellum, Posterior Lobe, Declive, Occipital     0     -1     0  
Lt. Frontal Lobe, Middle Frontal Gyrus     0     0     -1  
Lt. Sub-lobar, Insula     0     0     -1  
Rt. Frontal Lobe, Middle Frontal Gyrus     0     0     -1  
Rt. Frontal Lobe, Sub-gyral     0     0     -1  
Lt. Temporal Lobe, Fusiform Gyrus     0     0     -1  
Lt. Temporal Lobe, Inferior Temporal Gyrus     0     0     -1  
Lt. Temporal Lobe, Middle Temporal Gyrus     0     0     -1  
Rt. Temporal Lobe, Middle Temporal Gyrus     0     0     -1  
Rt. Limbic Lobe, Anterior Cingulate     0     0     -1  


Statistical Analysis 1 for Comparison of Changes in Brain Glucose Metabolism Using by Brain 18F-FDG PET: Increased and Decreased Areas of Brain Glucose Metabolism
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] 0.05
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  In our analysis, the null hypothesis is that the effects of three experimental groups are same each other, and the alternative hypothesis is that the therapeutic effect of combination intervention Group (Umbilical Cord Blood + Erythropoietin + Rehabilitation) has much higher than that of either Erythropoietin + Rehabilitation Group or Rehabilitation Group. This study is a pilot study and therefore, power calculation was not applicable in our study. The sample size of each group is more than 30.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Voxels with an uncorrected p-value of <0.05 were considered significant, and an extent threshold Ke of 100 voxels was set by SPM implanted in Matlab.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The baseline and post-therapy data of each group were compared using paired t-test statistics.



7.  Secondary:   Changes in Functional Performance in Daily Activities   [ Time Frame: Baseline -1 month - 3 months - 6 months ]

Measure Type Secondary
Measure Title Changes in Functional Performance in Daily Activities
Measure Description Pediatric Evaluation of Disability Inventory (PEDI) for assessing functional performance in daily activities in children (All values are adjusted and higher value means better functional performance, 0 - worst, 100 - best). We reported here 2 scales and 3 domains of each scale: a Functional Skill Scale (FSS) and a Caregiver Assistance Scale (CAS) which are divided respectively into 3 domains: self care, mobility, and social function. Categories of outcome table are each domain scores measured at each assessment time point.
Time Frame Baseline -1 month - 3 months - 6 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  31     33     32  
Changes in Functional Performance in Daily Activities  
[units: units on a scale]
Mean ± Standard Error
     
Self care of FSS: Baseline     39.1  ± 2.5     38.2  ± 2.7     37.4  ± 2.2  
Self care of FSS: 1 month     42.2  ± 2.2     40.4  ± 2.9     40.0  ± 2.2  
Self care of FSS: 3 months     44.7  ± 2.4     43.5  ± 2.9     41.7  ± 2.3  
Self care of FSS: 6 months     46.5  ± 2.5     45.0  ± 2.8     42.8  ± 2.3  
Mobility of FSS: Baseline     24.8  ± 3.7     29.2  ± 4.3     24.9  ± 3.7  
Mobility of FSS: 1 month     28.1  ± 3.9     32.4  ± 4.3     27.9  ± 3.8  
Mobility of FSS: 3 months     31.7  ± 4.3     34.6  ± 4.3     29.3  ± 3.9  
Mobility of FSS: 6 months     34.6  ± 4.3     36.6  ± 4.4     31.4  ± 3.9  
Social function of FSS: Baseline     40.0  ± 3.5     40.1  ± 3.3     34.8  ± 3.5  
Social function of FSS: 1 month     42.8  ± 3.6     42.5  ± 3.3     37.5  ± 3.6  
Social function of FSS: 3 months     46.4  ± 3.9     45.8  ± 3.3     40.0  ± 3.5  
Social function of FSS: 6 months     49.1  ± 3.6     47.8  ± 3.4     42.3  ± 3.9  
Self care of CAS: Baseline     18.0  ± 4.1     17.9  ± 3.7     15.3  ± 3.2  
Self care of CAS: 1 month     20.1  ± 4.0     21.1  ± 3.8     19.0  ± 3.7  
Self care of CAS: 3 months     27.0  ± 4.3     24.2  ± 3.9     21.5  ± 3.7  
Self care of CAS: 6 months     29.4  ± 4.0     26.0  ± 4.1     23.1  ± 3.9  
Mobility of CAS: Baseline     14.6  ± 4.1     19.7  ± 4.8     13.5  ± 4.0  
Mobility of CAS: 1 month     19.6  ± 4.5     22.6  ± 4.9     15.6  ± 4.2  
Moblity of CAS: 3 months     22.5  ± 5.1     26.0  ± 5.3     19.3  ± 4.5  
Mobility of CAS: 6 months     24.9  ± 5.5     29.2  ± 5.4     24.0  ± 4.8  
Social function of CAS: Baseline     23.0  ± 5.2     24.7  ± 3.9     18.2  ± 4.4  
Social function of CAS: 1 month     28.5  ± 5.6     30.0  ± 4.5     21.1  ± 4.8  
Social function of CAS: 3 months     34.8  ± 6.0     34.2  ± 4.8     24.2  ± 5.0  
Social function of CAS: 6 months     38.4  ± 6.2     36.2  ± 4.6     27.6  ± 5.3  

No statistical analysis provided for Changes in Functional Performance in Daily Activities



8.  Secondary:   Changes in Functional Independence in Daily Activities   [ Time Frame: Baseline - 1 month - 3 months - 6 months ]

Measure Type Secondary
Measure Title Changes in Functional Independence in Daily Activities
Measure Description WeeFIM (Functional Independence Measure for Children) measures functional independence in daily activities. WeeFIM contains 18 items and each item is ranked from complete dependence (scored as 1) to complete independence (scored as 7). The range is from 18 to 126 and higher scores mean more independent performance in daily activities. Categories of outcome table are total WeeFIM scores measured at each assessment time point.
Time Frame Baseline - 1 month - 3 months - 6 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  31     33     32  
Changes in Functional Independence in Daily Activities  
[units: units on a scale]
Mean ± Standard Error
     
Baseline     34.1  ± 3.8     36.6  ± 3.7     31.4  ± 2.9  
1 month     35.6  ± 4.1     37.5  ± 3.8     33.2  ± 3.1  
3 months     38.7  ± 4.7     38.5  ± 4.1     37.1  ± 3.8  
6 months     41.1  ± 4.8     40.3  ± 4.2     37.7  ± 4.1  


Statistical Analysis 1 for Changes in Functional Independence in Daily Activities
Groups [1] All groups
Method [2] Repeated Measure ANOVA
P Value [3] <0.05
Wilks' Lambda (group*visit effect) [4] 1.279
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  In our analysis, the null hypothesis is that the effects of 3 experimental groups are same, and the alternative hypothesis is that the therapeutic effect of combination intervention Group (Umbilical Cord Blood + Erythropoietin + Rehabilitation) is higher than that of either Erythropoietin + Rehabilitation or Rehabilitation Group. This is a pilot study and power calculation was not applicable. The sample size of each group is over 30 and is considered to follow approximately normal distribution.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



9.  Secondary:   Changes in Muscle Strength   [ Time Frame: Baseline - 1 month - 3 months - 6 months ]

Measure Type Secondary
Measure Title Changes in Muscle Strength
Measure Description Summation of MMT (manual muscle strength test score): summated scores of the manual muscle strength test (zero=0, trace=1, poor=2, fair=3, good=4, normal=5) for flexors, extensors, abductors, and adductors of bilateral shoulder and hip joints; flexors and extensors of bilateral elbow, wrist, and knee; dorsiflexors and plantar flexors of the ankles (range: 0 ~ 160) Higher score means better muscle strength. Categories of outcome table are summation of MMT scores measured at each assessment time point.
Time Frame Baseline - 1 month - 3 months - 6 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  31     33     32  
Changes in Muscle Strength  
[units: units on a scale]
Mean ± Standard Error
     
Baseline     100.7  ± 5.5     104.8  ± 4.4     100.3  ± 4.6  
1 month     105.0  ± 4.9     106.8  ± 4.5     101.8  ± 4.6  
3 months     107.8  ± 4.4     107.7  ± 4.5     103.6  ± 4.6  
6 months     109.9  ± 4.6     109.3  ± 4.5     104.3  ± 4.6  


Statistical Analysis 1 for Changes in Muscle Strength
Groups [1] All groups
Method [2] Repeated Measure ANOVA
P Value [3] <0.05
Wilks' Lambda (group*visit effect) [4] 0.996
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  In our analysis, the null hypothesis is that the effects of 3 experimental groups are same, and the alternative hypothesis is that the therapeutic effect of combination intervention Group (Umbilical Cord Blood + Erythropoietin + Rehabilitation) is higher than that of either Erythropoietin + Rehabilitation or Rehabilitation Group. This is a pilot study and power calculation was not applicable. The sample size of each group is over 30 and is considered to follow approximately normal distribution.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



10.  Secondary:   Changes in Hand Function   [ Time Frame: Baseline - 1 month - 3 months - 6 months ]

Measure Type Secondary
Measure Title Changes in Hand Function
Measure Description QUEST (Quality of Upper Extremity Skills Test) as a standardized measurement tool for assessing hand function consisting of sub-scales; dissociated movement, grasps, weight bearing, and protective extension. These are standardized to range from zero (or below zero in grasp section) to 100 and higher values mean better hand function. We reported QUEST differences between each assessment times.
Time Frame Baseline - 1 month - 3 months - 6 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  31     33     32  
Changes in Hand Function  
[units: units on a scale]
Mean ± Standard Error
     
Baseline     36.0  ± 6.4     52.8  ± 4.9     43.0  ± 5.5  
1 month - Baseline     5.0  ± 1.4     5.7  ± 1.7     6.6  ± 1.4  
3 months - Baseline     11.1  ± 2.2     8.8  ± 2.0     10.5  ± 1.8  
6 months - Baseline     13.9  ± 2.6     10.7  ± 2.2     13.0  ± 2.4  
3 months - 1 month     5.7  ± 1.6     3.1  ± 1.0     3.5  ± 1.7  
6 months - 1 month     8.4  ± 2.0     5.1  ± 1.3     6.4  ± 2.1  
6 months - 3 months     2.8  ± 0.8     2.4  ± 0.8     3.1  ± 1.2  


Statistical Analysis 1 for Changes in Hand Function
Groups [1] All groups
Method [2] Repeated Measure ANOVA
P Value [3] <0.05
Wilks' Lambda (group*visit effect) [4] 0.56
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  In our analysis, the null hypothesis is that the effects of 3 experimental groups are same, and the alternative hypothesis is that the therapeutic effect of combination intervention Group (Umbilical Cord Blood + Erythropoietin + Rehabilitation) is higher than that of either Erythropoietin + Rehabilitation or Rehabilitation Group. This is a pilot study and power calculation was not applicable. The sample size of each group is over 30 and is considered to follow approximately normal distribution.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



11.  Secondary:   Number of Participants With Serious Adverse Events as a Measure of Safety,Which Are Related to Umbilical Cord Blood, Erythropoietin, or Immunosuppressant   [ Time Frame: 6 months ]

Measure Type Secondary
Measure Title Number of Participants With Serious Adverse Events as a Measure of Safety,Which Are Related to Umbilical Cord Blood, Erythropoietin, or Immunosuppressant
Measure Description The number of patients with serious adverse events within each group; Serious adverse events were defined as any event that resulted in death, was life-threatening, required hospitalization or prolonged the hospital stay, or was otherwise serious in the judgment of the investigator.
Time Frame 6 months  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation Allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg intravenously), Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times), and active rehabilitation
Erythropoietin & Rehabilitation Erythropoietin injection (twice a week for 4 weeks with the dosage of 500 IU/kg for 2 times intravenously and 250 IU/kg subcutaneously for 6 times),and active rehabilitation
Only Rehabilitation Active rehabilitation

Measured Values
    Umbilical Cord Blood & Erythropoietin & Rehabilitation     Erythropoietin & Rehabilitation     Only Rehabilitation  
Number of Participants Analyzed  
[units: participants]
  31     33     32  
Number of Participants With Serious Adverse Events as a Measure of Safety,Which Are Related to Umbilical Cord Blood, Erythropoietin, or Immunosuppressant  
[units: participants]
  3     3     3  


Statistical Analysis 1 for Number of Participants With Serious Adverse Events as a Measure of Safety,Which Are Related to Umbilical Cord Blood, Erythropoietin, or Immunosuppressant
Groups [1] All groups
Method [2] Fisher Exact
P Value [3] <0.05
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  We compared the ratio of participants with a certain adverse event (AE) and without the AE between three groups using Fisher Exact test.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  More Information