Allogeneic UCB Therapy With EPO in Children With CP

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Bundang CHA Hospital
Sponsor:
Collaborators:
Ministry of Health & Welfare, Korea
LG Life Sciences
Chong Kun Dang Pharmaceutical
CHA University
Information provided by (Responsible Party):
MinYoung Kim, M.D., Bundang CHA Hospital
ClinicalTrials.gov Identifier:
NCT01991145
First received: November 17, 2013
Last updated: NA
Last verified: November 2013
History: No changes posted
  Purpose

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.


Condition Intervention
Cerebral Palsy
Procedure: Umbilical Cord Blood therapy
Biological: Erythropoietin alfa
Other: Rehabilitation
Procedure: Placebo UCB
Biological: Placebo EPO

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
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

Resource links provided by NLM:


Further study details as provided by Bundang CHA Hospital:

Primary Outcome Measures:
  • Changes in Standardized Gross Motor Function [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    Muscle spasticity of biceps, hip adductors, hamstrings and heel cords is graded according to modified Ashworth scale (MAS).

  • Changes in Dynamic Component of Spasticity [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    Dynamic component of spasticity in bilateral hamstrings is graded using modified Tardieu scale (MTS).

  • Changes in Muscle Strength [ Time Frame: Baseline - 1 month - 3 months - 6 months - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline - 12 months ] [ Designated as safety issue: No ]
    Electroencephalography (EEG) will be performed twice prior to and 12 months after UCB therapy.

  • Changes in EP [ Time Frame: Baseline - 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 120
Study Start Date: November 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: UCB and EPO
UCB + EPO + Rehabilitation
Procedure: Umbilical Cord Blood therapy
HLA (Human Leukocyte Antigen) typing
Biological: Erythropoietin alfa
Other Name: Espogen (LG Life Science Ltd.)
Other: Rehabilitation
Active rehabilitation
Active Comparator: UCB and placebo EPO
UCB + placebo EPO + Rehabilitation
Procedure: Umbilical Cord Blood therapy
HLA (Human Leukocyte Antigen) typing
Other: Rehabilitation
Active rehabilitation
Biological: Placebo EPO
Active Comparator: placebo UCB and EPO
placebo UCB + EPO + Rehabilitation
Biological: Erythropoietin alfa
Other Name: Espogen (LG Life Science Ltd.)
Other: Rehabilitation
Active rehabilitation
Procedure: Placebo UCB
Placebo Comparator: placebo UCB and placebo EPO
placebo UCB + placebo EPO + Rehabilitation
Other: Rehabilitation
Active rehabilitation
Procedure: Placebo UCB Biological: Placebo EPO

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.

  Eligibility

Ages Eligible for Study:   10 Months to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01991145

Contacts
Contact: MinYoung Kim, M.D., Ph.D. 82-31-780-6281 kmin@cha.ac.kr
Contact: Kyunghoon Min, M.D. 82-31-780-6281 minkh@chamc.co.kr

Locations
Korea, Republic of
CHA Bundang Medical Center, CHA University Recruiting
Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-712
Contact: MiYoung Jung    82-31-780-2954    mi-young80@chamc.co.kr   
Contact: Sunhee Lee    82-31-780-6205    murkogi0@chamc.co.kr   
Principal Investigator: MinYoung Kim, M.D., Ph.D.         
Sub-Investigator: Myung Seo Kang, M.D., Ph.D.         
Sub-Investigator: Moon Kyu Kim, M.D., Ph.D.         
Sub-Investigator: Sang Heum Kim, M.D.         
Sub-Investigator: Su Jin Jang, M.D.         
Sub-Investigator: Kyunghoon Min, M.D.         
Sub-Investigator: Ji Young Lee, M.D.         
Sub-Investigator: Jooyeon Ko, P.T., Ph.D.         
Sub-Investigator: Hee Song Lee, M.D.         
Sub-Investigator: Jae Sun Shim, M.D.         
Sub-Investigator: Seung Hoon Lee, M.D.         
Sub-Investigator: Yoongul Oh, M.D.         
Sub-Investigator: Sunyoung Park, P.T.         
Sub-Investigator: Boram Shin, P.T.         
Sub-Investigator: Myounghee Hong, P.T.         
Sub-Investigator: Eunmin Noh, P.T.         
Sub-Investigator: Jeewoon Jung, P.T.         
Sub-Investigator: Eun Young Park, O.T.         
Sub-Investigator: Ha Jin Lim, O.T.         
Sub-Investigator: Hye Kyung Lim, O.T.         
Sub-Investigator: Yun Rim Jeon, O.T.         
Sponsors and Collaborators
MinYoung Kim, M.D.
Ministry of Health & Welfare, Korea
LG Life Sciences
Chong Kun Dang Pharmaceutical
CHA University
Investigators
Principal Investigator: MinYoung Kim, M.D., Ph.D. CHA University
  More Information

No publications provided

Responsible Party: MinYoung Kim, M.D., Professor of CHA University, M.D., Ph.D., Bundang CHA Hospital
ClinicalTrials.gov Identifier: NCT01991145     History of Changes
Other Study ID Numbers: UCBnEPOinCP
Study First Received: November 17, 2013
Last Updated: November 17, 2013
Health Authority: Korea: Institutional Review Board
Korea: Food and Drug Administration
Korea: Ministry for Health, Welfare and Family Affairs

Keywords provided by Bundang CHA Hospital:
Cerebral Palsy
Umbilical Cord Blood
Erythropoietin
Rehabilitation

Additional relevant MeSH terms:
Cerebral Palsy
Brain Damage, Chronic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Epoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014