Is Autologous Umbilical Cord Blood Reinfusion Beneficial in Children With Cerebral Palsy: A Randomized, Blinded, Placebo-Controlled, Crossover Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 63
- 试验地点
- 2
- 主要终点
- Change in Gross Motor Function Measure 66 (GMFM-66) Score
研究概览
简要总结
The purpose of this study is to determine the efficacy of a single intravenous infusion of autologous umbilical cord blood (UCB) for the treatment of pediatric patients with spastic cerebral palsy.
详细描述
Cerebral palsy results from in utero or perinatal injury to the developing brain, often through stroke, hypoxic insult or hemorrhage. Currently available treatments for patients with cerebral palsy are supportive, but not curative. Umbilical cord blood (UCB) has been shown to lessen the clinical and radiographic impact of hypoxic brain injury and stroke in animal models. UCB also engrafts and differentiates in brain, facilitating neural cell repair, in animal models and human patients with inborn errors of metabolism undergoing allogeneic, unrelated donor UCB transplantation. We hypothesize that, in the setting of brain injury, infusion of autologous UCB will facilitate neural cell repair resulting in improved function in pediatric patients with cerebral palsy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Months 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 12 months and ≤ 6 years
- •Diagnosis: Spastic cerebral palsy with diplegia, hemiplegia, or quadraplegia.
- •Performance status:
- •Gross Motor Function (GMF) Classification Score levels II - IV or GMF Score leve I, age >/= 2 years Spastic hemiplegia: GMF Score II-IV or minimal functional capabilities in the affected upper extremity. A subject classified as GMFCS level I with significant upper extremity impairment will be eligible if the affected upper extremity is used as an assist only. An eligibility committee will meet to review the child's records and determine eligibility.
- •Bilateral hypotonic CP (diplegia or quadriplegia): GMF Score II-IV and an abnormal brain MRI suggestive of an acquired etiology (versus a genetic etiology or brain malformation).
- •Autologous umbilical cord blood available at a private or public cord blood bank with a minimum total nucleated cell dose of ≥ 1 x 107 cells/kilogram.
- •Parental consent.
排除标准
- •Athetoid cerebral palsy.
- •Autism and autistic spectrum disorders without motor disability.
- •Hypsarrhythmia.
- •Intractable seizures causing epileptic encephalopathy.
- •Evidence of a progressive neurologic disease.
- •Known HIV or uncontrolled bacterial, fungal, or viral infections.
- •Impaired renal or liver function as determined by serum creatinine >1.5mg/dL and/or total bilirubin >1.3mg/dL.
- •Head circumference >3 standard deviations below the mean for age.
- •Known genetic disease or phenotypic evidence of a genetic disease on physical examination.
- •Concurrent genetic or acquired disease or comorbidity(ies) that could require a future allogeneic stem cell transplant.
- •Requires ventilatory support, including home ventilator, CPAP, BiPAP, or supplemental oxygen.
- •Patient's medical condition does not permit safe travel.
- •Previously received any form of cellular therapy.
- •Autologous umbilical cord blood unit has any of the following:
- •Total nuclear cell dose < 1 x 107 cells/kilogram
- •Positive maternal infectious disease markers (except CMV)
- •Evidence of infectious contamination of the cord blood unit
- •Lack of a test sample to confirm identity
- •Evidence of a genetic disease
- •Unable to obtain parental consent.
研究组 & 干预措施
Autologous UCB Reinfusion First,Then Placebo
Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.
干预措施: Autologous UCB Reinfusion (Biological)
Autologous UCB Reinfusion First,Then Placebo
Subjects receive their autologous umbilical cord blood cells at Baseline, than placebo at Year 1.
干预措施: Placebo (Other)
Placebo First, Then Autologous UCB Reinfusion
Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
干预措施: Placebo (Other)
Placebo First, Then Autologous UCB Reinfusion
Subjects receive placebo at Baseline, then autologous umbilical cord blood cell reinfusion at Year 1.
干预措施: Autologous UCB Reinfusion (Biological)
结局指标
主要结局
Change in Gross Motor Function Measure 66 (GMFM-66) Score
时间窗: Baseline to Year 1
Change in Gross Motor Function Measure 66 (GMFM-66) Score from Baseline to Year 1. The GMFM-66 is a clinical tool used to evaluate gross motor function in children with cerebral palsy and is scored using a propriety software program called the Gross Motor Ability Estimator (GMAE) that produces an interval level continuous score ranging from 0 to 100. Higher scores indicate better motor function. A negative change in GMFM-66 score indicates a reduction in motor function, a positive change indicates improvement in motor function, and zero indicates no change in motor function.
次要结局
- Change in Peabody Gross Motor Quotient From Baseline to Year 1(Baseline to Year 1)
- Change in IT-QOL Questionnaire Score(Baseline to Year 1)
- Change in CP-QOL Score(Baseline, Year 1)
- Change in Whole Brain Connectivity Measured by Diffusion Tensor Magnetic Resonance Imaging (MRI)(Baseline to Year 1)
- Change in Loes Score of Functional MRI From Baseline to Year 1 and From Year 1 to Year 2(Baseline, Year 1, Year 2)
- Change in Bayley Scales of Infant and Toddler Development-III, Cognitive Composite From Baseline to Year 1(Baseline to Year 1)
- Change in Wechsler Preschool and Primary Scale of Intelligence (WPPSI) III Full Scale Intelligence Quotient (IQ) for Younger Children (Ages 2 Years & 6 Months to 3 Years & 11 Months) From Baseline to Year 1.(Baseline to Year 1)
- Change in the Wechsler Intelligence Scale for Children (WISC-IV) From Baseline to Year 1.(Baseline to Year 1)
- Change in Cognitive Z-Score From Baseline to Year 1(Baseline to Year 1)
- Change in Assisting Hand Assessment (AHA) Score From Baseline to Year 1(Baseline to Year 1)
- Change in Pediatric Evaluation of Disability (PEDI) Self Care Score(Baseline to Year 1)
- Change in Pediatric Evaluation of Disability (PEDI) Mobility Score(Baseline to Year 1)
- Change in Pediatric Evaluation of Disability (PEDI) Social Function Score(Baseline to Year 1)
- Change in Child Behavior Checklist (CBCL) Z-score Internalizing Problems From Baseline to Year 1(Baseline to Year 1)
- Change in Child Behavior Checklist (CBCL) Z-score Externalizing Problems From Baseline to Year 1(Baseline to Year 1)
- Change in Child Behavior Checklist (CBCL) Z-score Total Problems From Baseline to Year 1(Baseline to Year 1)
- Change in Parental Distress From Baseline to Year 1(Baseline to Year 1)
- Change in Parent-Child Dysfunctional Interaction From Baseline to Year 1(Baseline to Year 1)
- Change in Difficult Child Score From Baseline to Year 1(Baseline to Year 1)
- Modified Ashworth Scale at Baseline(Baseline)
- Modified Ashworth Scale at Year 1(Year 1)
- Change in Bruininks-Oseretsky-2 Total Motor Composite From Baseline to Year 1(Baseline to Year 1)
- Correlation Between Clinical Response and RNA Expression of Neural, Endothelial and Inflammatory Cytokines Measured by RNA Arrays in Cord Blood Cells Given to These Patients.(2 years)
- Parent Experience of Child Illness (PECI)(Baseline to Year 1)
研究者
Joanne Kurtzberg, MD
Professor of Pediatrics
Duke University