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

• ClinicalTrials.gov Identifier: NCT01988584
• Recruitment Status: Completed
• First Posted: November 20, 2013
• Results First Posted: November 21, 2022
• Last Update Posted: November 21, 2022
• 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
• Information provided by (Responsible Party): Charles Cox, The University of Texas Health Science Center, Houston

Tracking Information

• First Submitted Date: November 4, 2013
• First Posted Date: November 20, 2013
• Results First Submitted Date: October 29, 2020
• Results First Posted Date: November 21, 2022
• Last Update Posted Date: November 21, 2022
• Actual Study Start Date: November 2013
• Actual Primary Completion Date: February 21, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2022)

• Safety as Assessed by Number of Participants With In-hospital Infusion Toxicity [ Time Frame: 24 hours after infusion ]
  In-hospital infusion toxicity includes hemodynamic, pulmonary, hepatic, renal, or neurologic complications.
• Long-term Safety [ Time Frame: 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

Original Primary Outcome Measures (submitted: November 19, 2013)

To determine if autologous cells using either BMMNCs or hUCBs are safe to administer in children with CP by assessing change at multiple time points. [ Time Frame: All study visits from baseline to the end of study visit at year 2. ]

1. In-hospital infusion toxicity: pulmonary and hepatic function; new seizures, hemorrhagic lesions or ischemic lesions on imaging. (Composite Outcome Measure)
2. Long-term safety: development of new mass lesions or other pathological structural changes; worsening neurological status. (Composite Outcome Measure)

Current Secondary Outcome Measures (submitted: October 27, 2022)

• Number of Participants With an Improvement in White Matter Integrity. [ Time Frame: 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) [ Time Frame: baseline before 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-66) [ Time Frame: 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) [ Time Frame: baseline before 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.
• Gross Motor Function Classification Score (GMFM-88) [ Time Frame: 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 [ Time Frame: baseline before 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) - Communication [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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 [ Time Frame: baseline before 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 - Self-Care [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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 [ Time Frame: baseline before 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 - Recall [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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) [ Time Frame: baseline before 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.
• Expressive and Receptive Vocabulary as Assessed by Score on the Peabody Picture Vocabulary Test (PPVT-4) [ Time Frame: 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 [ Time Frame: baseline before 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) - Family [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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 [ Time Frame: baseline before 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 [ Time Frame: 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) [ Time Frame: baseline before infusion ]
  Standard scores ranging from 55 to 145 with higher scores indicating better outcomes and lower scores poorer outcomes.
• Visual-Spatial Processing as Assessed by Score on the Motor-Free Visual Perception Test (MVPT-3) [ Time Frame: 1 year after infusion ]
  Standard scores ranging from 55 to 145 with higher scores indicating better outcomes and lower scores poorer outcomes.

Original Secondary Outcome Measures (submitted: November 19, 2013)

To determine if late functional outcomes are improved following the administration of autologous cells compared with patients in the control group. [ Time Frame: Follow-up visits at 6 and 12 months, and the end of study year 2 visit. ]

1. Detailed analysis of MRI's done at baseline and follow-up visits. Specific white matter tract analysis will be identified at baseline MRI and correlated with motor function studies as the primary lesion of interest. Total volumes and specific tract lesions will be analyzed and correlated with functional outcomes.
2. The following functional outcomes studies will be performed at baseline, 6 months, 1 year after infusion, and 2 year after infusion.
   • Gross Motor Function Measures
   • Psychological Assessment Tests

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Effectiveness of Banked Cord Blood or Bone Marrow Stem Cells in Children With Cerebral Palsy (CP).
• Official Title: Autologous Cell Therapies for Cerebral Palsy-Chronic (ACT for CP)

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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Care Provider, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cerebral Palsy

Intervention

• Biological: umbilical cord blood (hUCB) cells
  Autologous umbilical cord blood banked with the Cord Blood Registry.
  Other Name: 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.
• Biological: bone marrow derived mononuclear cells (BMMNCs)
  Autologous stem cells from bone marrow harvest.
  Other Name: Autologous Stem Cells

Study Arms

• 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.
  Intervention: Biological: umbilical cord blood (hUCB) 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.
  Intervention: Biological: bone marrow derived mononuclear cells (BMMNCs)
• 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.
  Interventions:

  • Biological: umbilical cord blood (hUCB) cells
  • Drug: Saline Infusion (Placebo)
• Experimental: saline infusion (placebo), then bone marrow-derived mononuclear cells (BMMNCs)
  Interventions:

  • Drug: Saline Infusion (Placebo)
  • Biological: bone marrow derived mononuclear cells (BMMNCs)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 10, 2016): 20
• Original Estimated Enrollment (submitted: November 19, 2013): 30
• Actual Study Completion Date: February 21, 2018
• Actual Primary Completion Date: February 21, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 10 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01988584
• Other Study ID Numbers: HSC-MS-12-0876
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Charles Cox, The University of Texas Health Science Center, Houston
• Original Responsible Party: Same as current
• Current Study Sponsor: The University of Texas Health Science Center, Houston
• Original Study Sponsor: Same as current

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

• PRS Account: The University of Texas Health Science Center, Houston
• Verification Date: October 2022