A Randomized Study of Autologous Umbilical Cord Blood Reinfusion in Children With Cerebral Palsy

• A secondary objective is to determine effects on quality of life in these children. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• A secondary objective is to describe functional and morphologic changes on brain MRI in these children. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• A secondary objective is to ask whether there is a correlation between clinical response and RNA expression of neural, endotheial and inflammatory cytokines measured by RNA arrays in cord blood cells given to these patients. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

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.

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.

• Cerebral Palsy
• CP
• Spastic Cerebral Palsy

• Active Comparator: Autologous Umbilical Cord Blood Reinfusion
  All participants will be treated with autologous cord blood reinfusion, but the time course will vary between groups and participants will be blinded to the order in which they receive infusions.
  Intervention: Biological: Autologous Umbilical Cord Blood or Placebo
• Placebo Comparator: Placebo
  All participants will be treated with autologous cord blood reinfusion, but the time course will vary between groups and participants will be blinded to the order in which they receive infusions.
  Intervention: Biological: Autologous Umbilical Cord Blood or Placebo

Inclusion Criteria:

• Age ≥ 12 months and ≤ 6 years
• Diagnosis: Spastic cerebral palsy with diplegia, hemiplegia, or quadraplegia.
• Performance status: Gross Motor Function Classification Score levels II - IV as determined by the Gross Motor Function Measure-66 (see Appendix 1).
• 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.

Exclusion Criteria:

• 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:

  1. Total nuclear cell dose < 1 x 107 cells/kilogram
  2. Positive maternal infectious disease markers (except CMV)
  3. Evidence of infectious contamination of the cord blood unit
  4. Lack of a test sample to confirm identity
  5. Evidence of a genetic disease
• Unable to obtain parental consent.