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

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

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.

Study Overview

• Status: Completed
• Conditions: Cerebral Palsy
• Intervention / Treatment: Biological: umbilical cord blood (hUCB) cells; Biological: bone marrow derived mononuclear cells (BMMNCs); Drug: Saline Infusion (Placebo)

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • UTHealth, Medical School, Dept. of Pediatric Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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)
2. Gross Motor Function Classification Score level II-V
3. Ages 24 months to 10 years
4. English speaking, if verbal
5. Ability to travel to Houston for treatment and follow-up -

Exclusion Criteria:

1. 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]
2. 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
3. Normal brain MRI
4. 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
5. Progressing neurological disease (as defined by Batten Disease, Leukodystrophies, Metabolic disorders, Mitochondrial disorders, Neurotransmitter disorders)
6. Microcephaly, macrocephaly, cortical malformations, genetic disorders of dysgenesis brain malformations due to infection or metabolic disorders
7. Pulmonary disease requiring ventilator support
8. If hUCB candidate, banked cord cells totaling <10 million/kg
9. If hUCB candidate, any positive maternal infectious disease test (Hepatitis A, Hepatitis B, HIV 1, HIV 2, HTLV 1, HTLV 2, and Syphilis)
10. If hUCB candidate, cord blood sample contamination
11. Participation in a concurrent intervention study
12. Unwillingness to return for follow-up visits
13. Contraindications to MRI
14. Any patient that the investigators feel in their opinion the study intervention is unlikely to benefit the patient will be a screen failure.
15. Any patients who are currently or has previously been enrolled in a clinical stem cell study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: umbilical cord blood (UCB) cells; 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; Autologous umbilical cord blood banked with the Cord Blood Registry.; Other Names: Autolgous Stem Cells
Experimental: 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.	Biological: bone marrow derived mononuclear cells (BMMNCs); Autologous stem cells from bone marrow harvest.; Other Names: Autologous Stem Cells
Experimental: saline infusion (placebo), then umbilical cord blood (UCB) 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.	Biological: umbilical cord blood (hUCB) cells; Autologous umbilical cord blood banked with the Cord Blood Registry.; Other Names: Autolgous Stem Cells; Drug: Saline Infusion (Placebo); 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.
Experimental: saline infusion (placebo), then bone marrow-derived mononuclear cells (BMMNCs)	Biological: bone marrow derived mononuclear cells (BMMNCs); Autologous stem cells from bone marrow harvest.; Other Names: Autologous Stem Cells; Drug: Saline Infusion (Placebo); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Cord Blood Registry (CBR); Let's Cure CP Foundation; Mission Connect, a program of TIRR Foundation
• Investigators: Principal Investigator: Charles S Cox, MD, UTHealth, Medical School, Dept. of Pediatric Surgery

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2013
• Primary Completion (Actual): February 21, 2018
• Study Completion (Actual): February 21, 2018

Study Registration Dates

• First Submitted: November 4, 2013
• First Submitted That Met QC Criteria: November 19, 2013
• First Posted (Estimate): November 20, 2013

Study Record Updates

• Last Update Posted (Actual): November 21, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Cerebral Palsy; Stem Cells; Umbilical Cord Blood; Brain Injury; Bone Marrow; Mononuclear Cells
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Brain Damage, Chronic; Cerebral Palsy; Paralysis
• Other Study ID Numbers: HSC-MS-12-0876