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

Phase 2

Completed

Conditions: Cerebral Palsy

Interventions: Biological: umbilical cord blood (hUCB) cells
Biological: bone marrow derived mononuclear cells (BMMNCs)
Drug: Saline Infusion (Placebo)

Registration Number: NCT01988584

Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
umbilical cord blood (UCB) cells	umbilical cord blood (hUCB) cells	Children who have banked UCB with CBR will receive an umbilical cord blood stem cell infusion at the baseline/treatment visit.
bone marrow-derived mononuclear cells (BMMNCs)	bone marrow derived mononuclear cells (BMMNCs)	Children in the BMMNC group will undergo bone marrow harvest and stem cell infusion at the baseline/treatment visit.
saline infusion (placebo), then umbilical cord blood (UCB) cells	umbilical cord blood (hUCB) cells	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.
saline infusion (placebo), then umbilical cord blood (UCB) cells	Saline Infusion (Placebo)	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.
saline infusion (placebo), then bone marrow-derived mononuclear cells (BMMNCs)	Saline Infusion (Placebo)	-
saline infusion (placebo), then bone marrow-derived mononuclear cells (BMMNCs)	bone marrow derived mononuclear cells (BMMNCs)	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With an Improvement in White Matter Integrity.	from baseline to 1 year after infusion	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.
Gross Motor Function Classification Score (GMFM-66)	1 year after infusion	Interval age adjusted scaled scores from 0 to 100 with 0 reflecting a child with low motor ability and 100 indicating high motor ability.
Gross Motor Function Classification Score (GMFM-88)	1 year after infusion	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.
Score on Vineland Adaptive Behavior Scales (VABS-2) - Communication	1 year after infusion	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.
Score on Vineland Adaptive Behavior Scales (VABS-2) - Daily Living	1 year after infusion	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.
Score on Vineland Adaptive Behavior Scales (VABS-2) - Social	1 year after infusion	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.
Score on Vineland Adaptive Behavior Scales (VABS-2) - Motor	1 year after infusion	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.
Score on Pediatric Evaluation of Disability Inventory - Self-Care	1 year after infusion	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.
Score on Pediatric Evaluation of Disability Inventory - Mobility	1 year after infusion	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.
Score on Pediatric Evaluation of Disability Inventory - Social	1 year after infusion	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.
Score on A Developmental NEuroPSYchological Assessment (NEPSY-II) - Learning and Memory Memory Subtest - Recall	1 year after infusion	Scales scores from 1 to 19 with higher scores indicate better outcomes and lower scores indicate poorer outcomes.
Score on A Developmental NEuroPSYchological Assessment (NEPSY-II) - Learning and Memory Memory Subtest - Free/Cued	1 year after infusion	Scales scores from 1 to 19 with higher scores indicate better outcomes and lower scores indicate poorer outcomes.
Expressive and Receptive Vocabulary as Assessed by Score on the Peabody Picture Vocabulary Test (PPVT-4)	1 year after infusion	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.
Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Family	1 year after infusion	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.
Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Social	1 year after infusion	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.
Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Feelings	1 year after infusion	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.
Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Participation	1 year after infusion	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.
Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Emotional	1 year after infusion	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.
Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Access	1 year after infusion	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.
Score on Cerebral Palsy Quality of Life Questionnaire (CPQOL) - Pain	1 year after infusion	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.
Visual-Spatial Processing as Assessed by Score on the Motor-Free Visual Perception Test (MVPT-3)	1 year after infusion	Standard scores ranging from 55 to 145 with higher scores indicating better outcomes and lower scores poorer outcomes.