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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cerebral Palsy	Biological: umbilical cord blood (hUCB) cells; Drug: Saline Infusion (Placebo); Biological: bone marrow derived mononuclear cells (BMMNCs)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Autologous Cell Therapies for Cerebral Palsy-Chronic (ACT for CP)
• Actual Study Start Date: November 2013
• Actual Primary Completion Date: February 21, 2018
• Actual Study Completion Date: February 21, 2018

Arms and Interventions

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 Name: 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 Name: 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 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.
Experimental: saline infusion (placebo), then bone marrow-derived mononuclear cells (BMMNCs)	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

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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

Secondary Outcome Measures :

1. 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.

2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. 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.
40. 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.
41. 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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Texas

UTHealth, Medical School, Dept. of Pediatric Surgery

Houston, Texas, United States, 77030

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

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 Documents (Full-Text)

Documents provided by Charles Cox, The University of Texas Health Science Center, Houston:

Study Protocol and Statistical Analysis Plan  [PDF] October 23, 2017

More Information

• Responsible Party: Charles Cox, The Children's Fund Distinguished Professor, Department of Pediatric Surgery, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT01988584
• Other Study ID Numbers: HSC-MS-12-0876
• First Posted: November 20, 2013
• Results First Posted: November 21, 2022
• Last Update Posted: November 21, 2022
• Last Verified: October 2022

Keywords provided by Charles Cox, The University of Texas Health Science Center, Houston:

Cerebral Palsy; Brain Injury; Stem Cells; Mononuclear Cells; Bone Marrow; Umbilical Cord Blood

Additional relevant MeSH terms:

Paralysis; Cerebral Palsy; Neurologic Manifestations; Nervous System Diseases; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases