Allogenic Umbilical Cord Blood and Erythropoietin Combination Therapy for Cerebral Palsy

Double-blind Randomized Controlled Trial to Evaluate the Efficacy and Safety of a Combination Therapy of Allogenic Umbilical Cord Blood and Erythropoietin for Children With Cerebral Palsy

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

Study Overview

• Status: Completed
• Conditions: Cerebral Palsy
• Intervention / Treatment: Biological: Umbilical Cord Blood Infusion; Drug: Erythropoietin Injection; Other: Active Rehabilitation; Other: Placebo Umbilical Cord Blood; Other: Placebo Erythropoietin

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.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of
      • CHA Bundang Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Umbilical Cord Blood & Erythropoietin & Rehabilitation; Allogenic umbilical cord blood infusion, erythropoietin injection & active rehabilitation	Biological: Umbilical Cord Blood Infusion; The subjects will be undertaken allogeneic umbilical cord blood infusion (total nucleated cells > 3x10^7/kg) intravenously under non-myeloablative immunosuppression (maintaining blood level of cyclosporine as 100-200ng/mL for 1 month).; Other Names: Donated Umbilical Cord Blood Units from Affiliated Cord Blood Bank; Drug: Erythropoietin Injection; Erythropoietin will be given as the schedule of 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.; Other Names: Brand name of Erythropoietin: Espogen (made by LG Life Science); Other: Active Rehabilitation; All subjects should participate in active rehabilitation. They received two physical and occupational therapy sessions per day. Post discharge, each participant continued to receive rehabilitation therapy at least 3 days per week for additional 5 months.
Active Comparator: Erythropoietin & Rehabilitation; Erythropoietin injection, active rehabilitation	Drug: Erythropoietin Injection; Erythropoietin will be given as the schedule of 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.; Other Names: Brand name of Erythropoietin: Espogen (made by LG Life Science); Other: Active Rehabilitation; All subjects should participate in active rehabilitation. They received two physical and occupational therapy sessions per day. Post discharge, each participant continued to receive rehabilitation therapy at least 3 days per week for additional 5 months.; Other: Placebo Umbilical Cord Blood; Placebo Umbilical Cord Blood will be given except the Experimental arm. Placebo Umbilical Cord Blood was made using peripheral blood. Participants and Investigators maintained as blind.; Other Names: Placebo Umbilical Cord Blood that resembles cord blood in appearance was designed; : 1.5 to 3 ml of the subject's own blood was collected and mixed with 15 to 20 ml of albumin.
Placebo Comparator: Only Rehabilitation; Active rehabilitation	Other: Active Rehabilitation; All subjects should participate in active rehabilitation. They received two physical and occupational therapy sessions per day. Post discharge, each participant continued to receive rehabilitation therapy at least 3 days per week for additional 5 months.; Other: Placebo Umbilical Cord Blood; Placebo Umbilical Cord Blood will be given except the Experimental arm. Placebo Umbilical Cord Blood was made using peripheral blood. Participants and Investigators maintained as blind.; Other Names: Placebo Umbilical Cord Blood that resembles cord blood in appearance was designed; : 1.5 to 3 ml of the subject's own blood was collected and mixed with 15 to 20 ml of albumin.; Other: Placebo Erythropoietin; Placebo Erythropoietin containing Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Motor Performance	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.	Baseline -1 month - 3 months - 6 months
Changes in Standardized Gross Motor Function	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.	Baseline - 1 month - 3 months - 6 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sung Kwang Medical Foundation
• Investigators: Study Chair: Minyoung Kim, MD, PhD, CHA University

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: August 29, 2010
• First Submitted That Met QC Criteria: August 31, 2010
• First Posted (Estimate): September 2, 2010

Study Record Updates

• Last Update Posted (Actual): November 24, 2020
• Last Update Submitted That Met QC Criteria: November 6, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: stem cell; umbilical cord blood; cerebral palsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Brain Damage, Chronic; Cerebral Palsy; Paralysis; Hematinics; Epoetin Alfa
• Other Study ID Numbers: RCTUBSC; PBC09-095 (Other Identifier: IRB of CHA Bundang Medical Center)