Safety and Effectiveness of Banked Cord Blood or Bone Marrow Stem Cells in Children With Cerebral Palsy (CP).

Study Overview
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Brief Summary
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The purpose of this study is to compare the safety and effectiveness of two types of stem cells,(either banked cord blood or bone marrow), in children between the ages of 2 to 10 years with CP. 15 children with banked cord blood at CBR and 15 children without banked cord blood will be enrolled into the study. The study involves one baseline/treatment visit and 3 follow-up visits at 6 months, 12 months, and 2 years. Five children in each group will be randomized to a placebo control group at the baseline/treatment visit. Parents will not be told if their child received stem cells or a placebo until the 12 month follow-up visit. At that time parents may elect to have their child receive the stem cell treatment; either bone marrow harvest or umbilical cord blood if banked with CBR. All study visits will be conducted at the UTHealth Medical School and Children's Memorial Hermann Hospital in Houston, Texas. As of 1/21/2014 we have met our enrollment limit for children without banked cord blood undergoing bone marrow harvest for stem cells.

Official Title
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Autologous Cell Therapies for Cerebral Palsy-Chronic (ACT for CP)

Conditions
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Cerebral Palsy

Intervention / Treatment
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* Biological: umbilical cord blood (hUCB) cells
* Drug: Saline Infusion (Placebo)
* Biological: bone marrow derived mononuclear cells (BMMNCs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with diagnosis of Cerebral Palsy (spastic CP due to periventricular white matter damage or neonatal brain injury from perinatal stroke or intra-ventricular hemorrhage) Gross Motor Function Classification Score level II-V Ages 24 months to 10 years English speaking, if verbal Ability to travel to Houston for treatment and follow-up - Exclusion Criteria: Known history of: Intractable seizures Traumatic brain injury Genetic disorder (as demonstrated by newborn screening or genetic diagnostic testing) Recently treated or current infection Renal insufficiency or altered renal function (as defined by serum creatinine > 1.5 mg/dl at screening) Hepatic disease or altered liver function (as defined by SGPT > 150 U/L [non-contusion related], and/or T. Bilirubin >1.3 mg/dL at screening) HIV+ (as demonstrated by positive blood test) Immunosuppression (as defined by WBC <3,000 cells/ml at screening) Infectious related neurological injury Sensitivity to Ethylene Oxide (EtO) [found in fumigants and disinfectants] If Athetoid CP diagnosis, other etiologies such as degenerative, mitochondrial, and metabolic disorders must be excluded, and the outcome assessments must be able to be conducted to assess for potential treatment effects Normal brain MRI Evidence of acute illness at the time of infusion, such as, but not limited to, fever (temperature > 37.5 C), vomiting, diarrhea, wheezing or crackles Progressing neurological disease (as defined by Batten Disease, Leukodystrophies, Metabolic disorders, Mitochondrial disorders, Neurotransmitter disorders) Microcephaly, macrocephaly, cortical malformations, genetic disorders of dysgenesis brain malformations due to infection or metabolic disorders Pulmonary disease requiring ventilator support If hUCB candidate, banked cord cells totaling <10 million/kg If hUCB candidate, any positive maternal infectious disease test (Hepatitis A, Hepatitis B, HIV 1, HIV 2, HTLV 1, HTLV 2, and Syphilis) If hUCB candidate, cord blood sample contamination Participation in a concurrent intervention study Unwillingness to return for follow-up visits Contraindications to MRI Any patient that the investigators feel in their opinion the study intervention is unlikely to benefit the patient will be a screen failure. Any patients who are currently or has previously been enrolled in a clinical stem cell study.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: umbilical cord blood (UCB) cells<br>Children who have banked UCB with CBR will receive an umbilical cord blood stem cell infusion at the baseline/treatment visit. | Biological: umbilical cord blood (hUCB) cells<br>* Autologous umbilical cord blood banked with the Cord Blood Registry.<br>* Other names: Autolgous Stem Cells;|
| Experimental: bone marrow-derived mononuclear cells (BMMNCs)<br>Children in the BMMNC group will undergo bone marrow harvest and stem cell infusion at the baseline/treatment visit. | Biological: bone marrow derived mononuclear cells (BMMNCs)<br>* Autologous stem cells from bone marrow harvest.<br>* Other names: Autologous Stem Cells;|
| Experimental: saline infusion (placebo), then umbilical cord blood (UCB) cells<br>Five children in each group will be randomly assigned to receive an inactive substance (placebo) at the baseline/treatment visit. Parents will be given the opportunity to cross-over to either the umbilical cord blood or bone marrow harvest group at the one year visit. | Biological: umbilical cord blood (hUCB) cells<br>* Autologous umbilical cord blood banked with the Cord Blood Registry.<br>* Other names: Autolgous Stem Cells;Drug: Saline Infusion (Placebo)<br>* A total of 10 children (5 from each cohort) will be randomized to a placebo infusion at the baseline visit and then have the opportunity to cross-over to stem cell treatment at the 1yr. visit.<br>|
| Experimental: saline infusion (placebo), then bone marrow-derived mononuclear cells (BMMNCs)<br> | Drug: Saline Infusion (Placebo)<br>* A total of 10 children (5 from each cohort) will be randomized to a placebo infusion at the baseline visit and then have the opportunity to cross-over to stem cell treatment at the 1yr. visit.<br>Biological: bone marrow derived mononuclear cells (BMMNCs)<br>* Autologous stem cells from bone marrow harvest.<br>* Other names: Autologous Stem Cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as Assessed by Number of Participants With In-hospital Infusion Toxicity | In-hospital infusion toxicity includes hemodynamic, pulmonary, hepatic, renal, or neurologic complications. | 24 hours after infusion | 
| Long-term Safety | Long-term safety as assessed by number of participants who developed new mass lesions or other pathological structural changes or had worsening neurological status | from the time of infusion to 1 year after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Improvement in White Matter Integrity. | Number of participants with an improvement in white matter integrity as measured by diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) reconstruction of corticospinal tract (CST) radial diffusivity (RD). Improvement is defined as radial diffusivity (RD) decreased in at least one corticospinal tract (CST) reconstruction. | from baseline to 1 year after infusion | 
| Gross Motor Function Classification Score (GMFM-66) | Interval age adjusted scaled scores from 0 to 100 with 0 reflecting a child with low motor ability and 100 indicating high motor ability. | baseline before infusion | 
| Gross Motor Function Classification Score (GMFM-66) | Interval age adjusted scaled scores from 0 to 100 with 0 reflecting a child with low motor ability and 100 indicating high motor ability. | 1 year after infusion | 
| Gross Motor Function Classification Score (GMFM-88) | Ordinal age adjusted scaled raw and percent scores from 0 to 100 with 0 reflecting a child with low motor ability and 100 indicating high motor ability. | baseline before infusion | 
| Gross Motor Function Classification Score (GMFM-88) | Ordinal age adjusted scaled raw and percent scores from 0 to 100 with 0 reflecting a child with low motor ability and 100 indicating high motor ability. | 1 year after infusion | 
| Score on Vineland Adaptive Behavior Scales (VABS-2) - Communication | Standard score ranging from 20 to 140 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Vineland Adaptive Behavior Scales (VABS-2) - Communication | Standard score ranging from 20 to 140 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Vineland Adaptive Behavior Scales (VABS-2) - Daily Living | Standard score ranging from 20 to 140 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Vineland Adaptive Behavior Scales (VABS-2) - Daily Living | Standard score ranging from 20 to 140 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Vineland Adaptive Behavior Scales (VABS-2) - Social | Standard score ranging from 20 to 140 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Vineland Adaptive Behavior Scales (VABS-2) - Social | Standard score ranging from 20 to 140 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Vineland Adaptive Behavior Scales (VABS-2) - Motor | Standard score ranging from 20 to 140 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Vineland Adaptive Behavior Scales (VABS-2) - Motor | Standard score ranging from 20 to 140 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Pediatric Evaluation of Disability Inventory - Self-Care | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Pediatric Evaluation of Disability Inventory - Self-Care | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Pediatric Evaluation of Disability Inventory - Mobility | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Pediatric Evaluation of Disability Inventory - Mobility | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Pediatric Evaluation of Disability Inventory - Social | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Pediatric Evaluation of Disability Inventory - Social | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on A Developmental NEuroPSYchological Assessment (NEPSY-II) - Learning and Memory Memory Subtest - Recall | Scales scores from 1 to 19 with higher scores indicate better outcomes and lower scores indicate poorer outcomes. | baseline before infusion | 
| Score on A Developmental NEuroPSYchological Assessment (NEPSY-II) - Learning and Memory Memory Subtest - Recall | Scales scores from 1 to 19 with higher scores indicate better outcomes and lower scores indicate poorer outcomes. | 1 year after infusion | 
| Score on A Developmental NEuroPSYchological Assessment (NEPSY-II) - Learning and Memory Memory Subtest - Free/Cued | Scales scores from 1 to 19 with higher scores indicate better outcomes and lower scores indicate poorer outcomes. | baseline before infusion | 
| Score on A Developmental NEuroPSYchological Assessment (NEPSY-II) - Learning and Memory Memory Subtest - Free/Cued | Scales scores from 1 to 19 with higher scores indicate better outcomes and lower scores indicate poorer outcomes. | 1 year after infusion | 
| Expressive and Receptive Vocabulary as Assessed by Score on the Peabody Picture Vocabulary Test (PPVT-4) | Standard score ranging from 20 to 160. Higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Expressive and Receptive Vocabulary as Assessed by Score on the Peabody Picture Vocabulary Test (PPVT-4) | Standard score ranging from 20 to 160. Higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Family | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Family | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Social | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Social | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Feelings | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Feelings | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Participation | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Participation | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Emotional | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Emotional | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Access | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Access | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Pain | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | baseline before infusion | 
| Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Pain | Standard scores ranging from 0 to 100 with higher scores indicate a child with a higher level of functioning and lower scores indicate a lower level of functioning. | 1 year after infusion | 
| Visual-Spatial Processing as Assessed by Score on the Motor-Free Visual Perception Test (MVPT-3) | Standard scores ranging from 55 to 145 with higher scores indicating better outcomes and lower scores poorer outcomes. | baseline before infusion | 
| Visual-Spatial Processing as Assessed by Score on the Motor-Free Visual Perception Test (MVPT-3) | Standard scores ranging from 55 to 145 with higher scores indicating better outcomes and lower scores poorer outcomes. | 1 year after infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral Palsy, Brain Injury, Stem Cells, Mononuclear Cells, Bone Marrow, Umbilical Cord Blood