Allogenic Umbilical Cord Blood and Erythropoietin Combination Therapy for Cerebral Palsy

Not Applicable

Completed

Conditions: Cerebral Palsy

Interventions: Biological: Umbilical Cord Blood Infusion
Drug: Erythropoietin Injection
Other: Active Rehabilitation
Other: Placebo Umbilical Cord Blood
Other: Placebo Erythropoietin

Registration Number: NCT01193660

Lead Sponsor: Sung Kwang Medical Foundation

Brief Summary: This randomized control study is aimed to determine efficacy of umbilical cord blood and erythropoietin combination therapy for children with cerebral palsy.

Detailed Description: Cerebral palsy is a disorder of movement and posture that result from a nonprogressive lesion or injury of the immature brain. It is a leading cause of childhood onset disability through one's life. Umbilical cord blood(UCB) is suggested as therapeutic method for cerebral palsy which resulted from animal studies. Stem cells included in UCB is expected to exert therapeutic efficacy for functional recovery.

It is also suggested that erythropoietin is useful to repair neurological injury in brain. The main mechanism of erythropoietin is supposed to be neuroprotection and neurogenesis which would reinforce the effect of stem cell as well.

Although autologous umbilical cord would be safe, the children who have problems at birth seldom have autologous umbilical cord blood. Allogenic umbilical cord blood might be useful for these children if its effect is approved.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 105

Inclusion Criteria

Known cerebral palsy
Willing to comply with all study procedure

Exclusion Criteria

High risk of pneumonia or renal function deterioration after using of immunosuppressant
Presence of known genetic disease
Possibility of drug hypersensitivity which is related to this study remedy
History of previous cell therapy
Poor cooperation of guardian,including inactive attitude for rehabilitation
Intractable seizure disorder
Autism

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Umbilical Cord Blood & Erythropoietin & Rehabilitation	Erythropoietin Injection	Allogenic umbilical cord blood infusion, erythropoietin injection \& active rehabilitation
Erythropoietin & Rehabilitation	Erythropoietin Injection	Erythropoietin injection, active rehabilitation
Erythropoietin & Rehabilitation	Active Rehabilitation	Erythropoietin injection, active rehabilitation
Only Rehabilitation	Placebo Umbilical Cord Blood	Active rehabilitation
Umbilical Cord Blood & Erythropoietin & Rehabilitation	Umbilical Cord Blood Infusion	Allogenic umbilical cord blood infusion, erythropoietin injection \& active rehabilitation
Umbilical Cord Blood & Erythropoietin & Rehabilitation	Active Rehabilitation	Allogenic umbilical cord blood infusion, erythropoietin injection \& active rehabilitation
Erythropoietin & Rehabilitation	Placebo Umbilical Cord Blood	Erythropoietin injection, active rehabilitation
Only Rehabilitation	Active Rehabilitation	Active rehabilitation
Only Rehabilitation	Placebo Erythropoietin	Active rehabilitation

Primary Outcome Measures

Name	Time	Method
Changes in Standardized Gross Motor Function	Baseline - 1 month - 3 months - 6 months	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.
Changes in Motor Performance	Baseline -1 month - 3 months - 6 months	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.

Secondary Outcome Measures

Name	Time	Method
Changes in Brain MRI	Baseline - 6 months	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.
Changes in Functional Performance in Daily Activities	Baseline -1 month - 3 months - 6 months	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.
Changes in Muscle Strength	Baseline - 1 month - 3 months - 6 months	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.
Changes in Hand Function	Baseline - 1 month - 3 months - 6 months	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.
Changes in Cognitive Neurodevelopmental Outcome	Baseline -1 month - 3 months - 6 months	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.
Changes in Functional Independence in Daily Activities	Baseline - 1 month - 3 months - 6 months	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.
Number of Participants With Serious Adverse Events as a Measure of Safety,Which Are Related to Umbilical Cord Blood, Erythropoietin, or Immunosuppressant	6 months	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.
Changes in Motor Neurodevelopmental Outcome	Baseline - 1 month - 3 months - 6 months	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.
Comparison of Changes in Brain Glucose Metabolism Using by Brain 18F-FDG PET: Increased and Decreased Areas of Brain Glucose Metabolism	Baseline - 2 weeks	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.