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Allogeneic UCB Therapy With EPO in Children With CP

Primary Purpose

Cerebral Palsy

Status
Completed
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Umbilical Cord Blood therapy
Erythropoietin alfa
Rehabilitation
Placebo UCB
Placebo EPO
Sponsored by
MinYoung Kim, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cerebral Palsy focused on measuring Cerebral Palsy, Umbilical Cord Blood, Erythropoietin, Rehabilitation

Eligibility Criteria

10 Months - 6 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosed with cerebral palsy
  • Age of ≥10 months and ≤6 years
  • Mismatch in HLA-A, B, and DR ≤2, and total nucleated cell count ≥3x107/kg. If the cell count is less than given values, more than 1 unit could be used.
  • Hemoglobin ≤13.6 g/dL
  • Decision of participation in the study by and acquisition of informed consent from the subject's representative
  • Willingness and ability to be hospitalized according to the schedule specified in the protocol and continue the study for 12 months after study entry

Exclusion Criteria:

  • Current aspiration pneumonia
  • Known genetic disease
  • History of hypersensitivity reaction to any study drugs pertinent to the study
  • History of participation in any other study with stem cell
  • Prior treatment with EPO within 3 months prior to study entry
  • Known coagulopathy with family history of thrombosis or medical history of recurrent thrombosis
  • Patient with severe seizure disease who has clinical convulsion despite combination therapy with 3 or more agents
  • Uncontrolled hypertension defined as systolic blood pressure >115 mmHg and/or diastolic blood pressure >70 mmHg
  • Hepatic impairment defined as asparate aminotransferase (AST) >55 IU/L and/or alanine aminotransferase (ALT) >45 IU/L
  • Renal impairment defined as creatinine (Cr) ≥1.2 mg/dL
  • Absolute neutrophil count ≤500/dL
  • Presence of diagnosed or suspected malignant tumor and/or hematologic malignancy
  • Non-compliance with study visits specified in the protocol or unwillingness of care-giver due to lack of understanding of the patient

Sites / Locations

  • CHA Bundang Medical Center, CHA University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

UCB and EPO

UCB and placebo EPO

placebo UCB and EPO

placebo UCB and placebo EPO

Arm Description

UCB + EPO + Rehabilitation

UCB + placebo EPO + Rehabilitation

placebo UCB + EPO + Rehabilitation

placebo UCB + placebo EPO + Rehabilitation

Outcomes

Primary Outcome Measures

Changes in Standardized Gross Motor Function
GMFM (Gross Motor Function Measure) is 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).
Changes in Motor Performance
GMPM (Gross Motor Performance Measure) is 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).
Changes in Cognitive Neurodevelopmental Outcome
Korean version of Bayley Scale of Infant Development-II (K-BSID-II) Mental Scale (range: 0~178; worst: 0, best: 178)
Changes in Motor Neurodevelopmental Outcome
Korean version of Bayley Scale of Infant Development-II (K-BSID-II) Motor Scale (range: 0~112; worst: 0, best: 112)

Secondary Outcome Measures

Changes in Gross Motor Function Classification System
GMFCS (Gross Motor Function Classification System) is a five-level classification system based on self-initiated movement, with emphasis on sitting, transfers, and mobility (level I: walks without limitations, ll: walks with limitations, III: walks using a hand-held mobility device, IV: self-mobility with limitations, V: transported in a manual wheelchair).
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 score means more independent performance in daily activities.
Changes in Functional Performance in Daily Activities
Pediatric Evaluation of Disability Inventory (PEDI) is used to assess functional performance in daily activities in children (All values are adjusted and higher value means better functional performance, 0 - worst, 100 - best). PEDI consists of 2 scales such as Functional Skill Scale (FSS) and a Caregiver Assistance Scale (CAS) and each scale is composed of 3 domains including self care, mobility, and social function.
Changes in Upper Extremity Function
QUEST (Quality of Upper Extremity Skills Test) is a standardized measurement tool for assessing upper extremity function consisting of sub-scales; dissociated movement, grasps, weight bearing, and protective extension. QUEST ranges from 0 (or below 0 in grasp section) to 100 and higher values mean better upper extremity function.
Changes in Visual Perception Test
Visual perception function will be assessed with one of 3 tools such as DTVP (Developmental Test of Visual Perception), MVPT (Motor-free Visual Perception Test), and VMI (Visual-Motor Integration, Visual Perception and Motor Coordination). Higher value means better visual perception ability.
Changes in Selective Movement of Lower Extremity
SCALE (Selective Control Assessment of Lower Extremity) is a measurement tool of selective movement of hip, knee, ankle, subtalar joint and toes. Selective voluntary motor control is graded at each joint as normal (2 points), impaired (1 point) or unable (0 point).
Changes in Spasticity
Muscle spasticity of biceps, hip adductors, hamstrings and heel cords is graded according to modified Ashworth scale (MAS).
Changes in Dynamic Component of Spasticity
Dynamic component of spasticity in bilateral hamstrings is graded using modified Tardieu scale (MTS).
Changes in Muscle Strength
Muscle strength is measured using summated scores of manual muscle 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 stronger muscle power.
Changes in Brain MRI
Diffusion Tensor Image (DTI) of brain MRI (magnetic resonance imaging) provides quantitative information about the microscopic integrity of white matter. White matter normally possesses a high degree of diffusion anisotropy than gray matter. Fractional anisotropy (FA) will be measured and it ranges from 0 to 1. Higher FA value means more integrity of white matter.
Changes in Brain 18F-FDG PET
18F-FDG PET (Positron emission tomography with fluorine-18-fluorodeoxyglucose) imaging will be performed twice prior to and 12 months after UCB therapy.
Changes in EEG
Electroencephalography (EEG) will be performed twice prior to and 12 months after UCB therapy.
Changes in EP
Median, tibial somatosensory evoked potential (SEP), visual evoked potential (VEP), auditory evoked potential (AEP) will be performed twice prior to and 12 months after UCB therapy.
Number of adverse events and participants with those adverse events
The numbers of adverse events and subjects with those serious adverse events within each group; A serious adverse event is any untoward medical occurrence that at any dose: results in death or is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or causes a congenital anomaly/birth defect.

Full Information

First Posted
November 17, 2013
Last Updated
January 15, 2020
Sponsor
MinYoung Kim, MD, PhD
Collaborators
Ministry of Health & Welfare, Korea, LG Life Sciences, Chong Kun Dang Pharmaceutical, CHA University
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1. Study Identification

Unique Protocol Identification Number
NCT01991145
Brief Title
Allogeneic UCB Therapy With EPO in Children With CP
Official Title
Safety and Efficacy of Allogeneic Umbilical Cord Blood Therapy Combined With Erythropoietin in Children With Cerebral Palsy: a Double-blind, Randomized, Placebo-controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
November 26, 2013 (Actual)
Primary Completion Date
June 24, 2017 (Actual)
Study Completion Date
June 24, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
MinYoung Kim, MD, PhD
Collaborators
Ministry of Health & Welfare, Korea, LG Life Sciences, Chong Kun Dang Pharmaceutical, CHA University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This randomized controlled study aims to evaluate the efficacy and safety of allogeneic umbilical cord blood therapy combined with erythropoietin for children with cerebral palsy.
Detailed Description
Cerebral palsy (CP) is a group of neurodevelopmental conditions with abnormal movement and posture resulted from a non-progressive cerebral disturbance. It is the most common cause of motor disability in childhood. Most therapies are palliative rather than restorative. Umbilical cord blood (UCB) and erythropoetin (EPO) may be used as restorative approach for children with CP. Many experimental animal studies have revealed that UCB is beneficial to improve and repair neurological injuries. EPO is also known to have neuroprotective effects. Based on animal studies and some clinical trials, UCB is suggested as a potential therapy for children with CP. EPO is combined to add synergistic effects to UCB therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebral Palsy
Keywords
Cerebral Palsy, Umbilical Cord Blood, Erythropoietin, Rehabilitation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
92 (Actual)

8. Arms, Groups, and Interventions

Arm Title
UCB and EPO
Arm Type
Experimental
Arm Description
UCB + EPO + Rehabilitation
Arm Title
UCB and placebo EPO
Arm Type
Active Comparator
Arm Description
UCB + placebo EPO + Rehabilitation
Arm Title
placebo UCB and EPO
Arm Type
Active Comparator
Arm Description
placebo UCB + EPO + Rehabilitation
Arm Title
placebo UCB and placebo EPO
Arm Type
Placebo Comparator
Arm Description
placebo UCB + placebo EPO + Rehabilitation
Intervention Type
Procedure
Intervention Name(s)
Umbilical Cord Blood therapy
Intervention Description
HLA (Human Leukocyte Antigen) typing
Intervention Type
Biological
Intervention Name(s)
Erythropoietin alfa
Other Intervention Name(s)
Espogen (LG Life Science Ltd.)
Intervention Type
Other
Intervention Name(s)
Rehabilitation
Intervention Description
Active rehabilitation
Intervention Type
Procedure
Intervention Name(s)
Placebo UCB
Intervention Type
Biological
Intervention Name(s)
Placebo EPO
Primary Outcome Measure Information:
Title
Changes in Standardized Gross Motor Function
Description
GMFM (Gross Motor Function Measure) is 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).
Time Frame
Baseline - 1 month - 3 months - 6 months - 12months
Title
Changes in Motor Performance
Description
GMPM (Gross Motor Performance Measure) is 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).
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Cognitive Neurodevelopmental Outcome
Description
Korean version of Bayley Scale of Infant Development-II (K-BSID-II) Mental Scale (range: 0~178; worst: 0, best: 178)
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Motor Neurodevelopmental Outcome
Description
Korean version of Bayley Scale of Infant Development-II (K-BSID-II) Motor Scale (range: 0~112; worst: 0, best: 112)
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Secondary Outcome Measure Information:
Title
Changes in Gross Motor Function Classification System
Description
GMFCS (Gross Motor Function Classification System) is a five-level classification system based on self-initiated movement, with emphasis on sitting, transfers, and mobility (level I: walks without limitations, ll: walks with limitations, III: walks using a hand-held mobility device, IV: self-mobility with limitations, V: transported in a manual wheelchair).
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Functional Independence in Daily Activities
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 score means more independent performance in daily activities.
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Functional Performance in Daily Activities
Description
Pediatric Evaluation of Disability Inventory (PEDI) is used to assess functional performance in daily activities in children (All values are adjusted and higher value means better functional performance, 0 - worst, 100 - best). PEDI consists of 2 scales such as Functional Skill Scale (FSS) and a Caregiver Assistance Scale (CAS) and each scale is composed of 3 domains including self care, mobility, and social function.
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Upper Extremity Function
Description
QUEST (Quality of Upper Extremity Skills Test) is a standardized measurement tool for assessing upper extremity function consisting of sub-scales; dissociated movement, grasps, weight bearing, and protective extension. QUEST ranges from 0 (or below 0 in grasp section) to 100 and higher values mean better upper extremity function.
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Visual Perception Test
Description
Visual perception function will be assessed with one of 3 tools such as DTVP (Developmental Test of Visual Perception), MVPT (Motor-free Visual Perception Test), and VMI (Visual-Motor Integration, Visual Perception and Motor Coordination). Higher value means better visual perception ability.
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Selective Movement of Lower Extremity
Description
SCALE (Selective Control Assessment of Lower Extremity) is a measurement tool of selective movement of hip, knee, ankle, subtalar joint and toes. Selective voluntary motor control is graded at each joint as normal (2 points), impaired (1 point) or unable (0 point).
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Spasticity
Description
Muscle spasticity of biceps, hip adductors, hamstrings and heel cords is graded according to modified Ashworth scale (MAS).
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Dynamic Component of Spasticity
Description
Dynamic component of spasticity in bilateral hamstrings is graded using modified Tardieu scale (MTS).
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Muscle Strength
Description
Muscle strength is measured using summated scores of manual muscle 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 stronger muscle power.
Time Frame
Baseline - 1 month - 3 months - 6 months - 12 months
Title
Changes in Brain MRI
Description
Diffusion Tensor Image (DTI) of brain MRI (magnetic resonance imaging) provides quantitative information about the microscopic integrity of white matter. White matter normally possesses a high degree of diffusion anisotropy than gray matter. Fractional anisotropy (FA) will be measured and it ranges from 0 to 1. Higher FA value means more integrity of white matter.
Time Frame
Baseline - 12 months
Title
Changes in Brain 18F-FDG PET
Description
18F-FDG PET (Positron emission tomography with fluorine-18-fluorodeoxyglucose) imaging will be performed twice prior to and 12 months after UCB therapy.
Time Frame
Baseline - 12 months
Title
Changes in EEG
Description
Electroencephalography (EEG) will be performed twice prior to and 12 months after UCB therapy.
Time Frame
Baseline - 12 months
Title
Changes in EP
Description
Median, tibial somatosensory evoked potential (SEP), visual evoked potential (VEP), auditory evoked potential (AEP) will be performed twice prior to and 12 months after UCB therapy.
Time Frame
Baseline - 12 months
Title
Number of adverse events and participants with those adverse events
Description
The numbers of adverse events and subjects with those serious adverse events within each group; A serious adverse event is any untoward medical occurrence that at any dose: results in death or is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or causes a congenital anomaly/birth defect.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Months
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosed with cerebral palsy Age of ≥10 months and ≤6 years Mismatch in HLA-A, B, and DR ≤2, and total nucleated cell count ≥3x107/kg. If the cell count is less than given values, more than 1 unit could be used. Hemoglobin ≤13.6 g/dL Decision of participation in the study by and acquisition of informed consent from the subject's representative Willingness and ability to be hospitalized according to the schedule specified in the protocol and continue the study for 12 months after study entry Exclusion Criteria: Current aspiration pneumonia Known genetic disease History of hypersensitivity reaction to any study drugs pertinent to the study History of participation in any other study with stem cell Prior treatment with EPO within 3 months prior to study entry Known coagulopathy with family history of thrombosis or medical history of recurrent thrombosis Patient with severe seizure disease who has clinical convulsion despite combination therapy with 3 or more agents Uncontrolled hypertension defined as systolic blood pressure >115 mmHg and/or diastolic blood pressure >70 mmHg Hepatic impairment defined as asparate aminotransferase (AST) >55 IU/L and/or alanine aminotransferase (ALT) >45 IU/L Renal impairment defined as creatinine (Cr) ≥1.2 mg/dL Absolute neutrophil count ≤500/dL Presence of diagnosed or suspected malignant tumor and/or hematologic malignancy Non-compliance with study visits specified in the protocol or unwillingness of care-giver due to lack of understanding of the patient
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MinYoung Kim, M.D., Ph.D.
Organizational Affiliation
CHA University
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHA Bundang Medical Center, CHA University
City
Seongnam-si
State/Province
Gyeonggi-do
ZIP/Postal Code
463-712
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
33246489
Citation
Min K, Suh MR, Cho KH, Park W, Kang MS, Jang SJ, Kim SH, Rhie S, Choi JI, Kim HJ, Cha KY, Kim M. Potentiation of cord blood cell therapy with erythropoietin for children with CP: a 2 x 2 factorial randomized placebo-controlled trial. Stem Cell Res Ther. 2020 Nov 27;11(1):509. doi: 10.1186/s13287-020-02020-y.
Results Reference
derived

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Allogeneic UCB Therapy With EPO in Children With CP

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