Treatment of Children With Cerebral Palsy With Autologous Umbilical Cord Blood, a Pilot Study

• ClinicalTrials.gov Identifier: NCT04243408
• Recruitment Status: Not yet recruiting
• First Posted: January 28, 2020
• Last Update Posted: January 31, 2020
• Sponsor: Sheba Medical Center
• Information provided by (Responsible Party): Dr. Omer Bar-Yosef, Sheba Medical Center

Study Description

Brief Summary:

This study is a phase II, prospective, double blind, placebo-controlled study of the efficacy of autologous umbilical cord blood infusion.

The study population will consist of 72 children ages 2 months to 12 years with cerebral palsy. The population will be randomly assigned to 2 groups, 36 children in each group. The study group be treated by cord blood in the beginning of the study and the control group by placebo product. The study population will be stratified to reduce variance 3 groups by age: 2-12 months / 1-6 years / 6-12 years The study will consist of 4 stages Stage 1: initial assessment by physiotherapist and occupational therapist / treatment by cord blood or placebo / blood work before and after treatment Stage 2: at stage 1 + 3 months assessment by physiotherapist and occupational therapist Stage 3: at stage 1 + 6 months assessment by physiotherapist and occupational therapist / cross-over treatment by cord blood or placebo / blood work before and after treatment Stage 4: at stage 1 + 12 months assessment by physiotherapist and occupational therapist The primary outcome is improvement motor skills six months after treatment at stage 3

Condition or disease	Intervention/treatment	Phase
Cerebral Palsy	Other: Autologous umbilical cord blood transfusion; Other: placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

This study is a phase II, prospective, double blind, placebo-control study of the efficacy of autologous umbilical cord blood infusion.

The study population will consist of 72 children ages 2 months to 12 years with cerebral palsy. The population will be randomly assigned to 2 groups, the study group be treated by cord blood in the beginning of the study and the control group by placebo product.

The study population will be stratified to reduce variance 3 groups by age: 2-12 months / 1-6 years / 6-12 years The study will consist of 4 stages Stage 1: initial assessment by physiotherapist and occupational therapist / treatment by cord blood or placebo / blood work before and after treatment Stage 2: at stage 1 + 3 months assessment by physiotherapist and occupational therapist Stage 3: at stage 1 + 6 months assessment by physiotherapist and occupational therapist

• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The randomization will be done by external source and the assignment will disclosed to cord bank bank only. They will produce either a cord blood or placebo unit which will be completely covered. Each unit will have its own index number that will be documented by the research coordinator. Neither the researcher or the family will know the nature of the unit.
• Primary Purpose: Treatment
• Official Title: Treatment of Children With Cerebral Palsy With Autologous Umbilical Cord Blood, a Pilot Study
• Estimated Study Start Date: January 2020
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: group 1	Other: Autologous umbilical cord blood transfusion; single dose of an autologous umbilical cord blood transfusion
Placebo Comparator: group 2	Other: placebo; The placebo product will consist of the standard ingredients of the acellular content of the UCB unit. It will consist of 20 ml Dextran (Plander 40.000 - 50g/500ml, solution for infusion) and 20 ml of human Albumin 5% (solution for infusion). The volume of placebo product will be 40 ml

Outcome Measures

Primary Outcome Measures :

1. Motor developmental improvement [ Time Frame: 6 months ]
   Gross Motor Function Measurement - 66 (GMFM-66). All score are normalized with mean 100 and STD of 15. High score is better than low score .
2. Motor developmental improvement [ Time Frame: 6 months ]
   Peabody developmental motor scales-second edition (PDMS-2). All score are normalized with mean 100 and STD 10. High score is better
3. Functional assessment [ Time Frame: 6 months ]
   Pediatric Evaluation of Disability Evaluation . Score 0-100 higher score better functionality Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT)

Secondary Outcome Measures :

1. Functional assessment [ Time Frame: 6 months ]
   Adaptive Behavior Assessment System, Third Edition (ABAS-3). All score are normalized with mean 100 and STD of 10. High score is better than low score .
2. Functional assessment [ Time Frame: 6 months ]
   Vineland Adaptive Behavior Scales—Second Edition (VINELAND-II). All score are normalized with mean 100 and STD of 15. High score is better than low score .

Eligibility Criteria

• Ages Eligible for Study: 2 Months to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 2 month and ≤ 12 years.

• Performance status for children older than 2 months and younger than 12 months including all the following (Gross Motor Function Classification Score is less indicative before 12 months):

  • Abnormal General Movements (in infants 2-6 months)
  • Abnormal Hammersmith Infant Neurological Examination

• Performance status for children older than 12 months

  • Bilateral spastic cerebral palsy (diplegia or quadraplegia): Gross Motor Function Classification Score levels I - IV
  • Spastic hemiplegia: Gross Motor Function Classification Score levels I - IV. A subject classified as GMFCS level I with significant upper extremity impairment will be eligible if the affected upper extremity is used as an assist only.
  • Bilateral hypotonic cerebral palsy (diplegia or quadraplegia): Gross Motor Function Classification Score levels I - IV.
• An abnormal brain MRI suggestive of an acquired etiology (and not genetic etiology or brain malformation).
• 4. Autologous umbilical cord blood available at a private or public cord blood bank with a minimum total nucleated cell dose of ≥ 2 x 10e7 cells/kilogram.
• 5. Parental consent.

Exclusion Criteria:

• Autism and autistic spectrum disorders without motor disability.
• Hypsarrhythmia.
• Intractable seizures causing epileptic encephalopathy.
• Evidence of a progressive neurologic disease.
• Known HIV or uncontrolled bacterial, fungal, or viral infections.
• Impaired renal or liver function as determined by serum creatinine >1.5mg/dL and/or total bilirubin >1.3mg/dL.
• Head circumference >3 standard deviations below the mean for age.
• Known genetic disease or phenotypic evidence of a genetic disease on physical examination.
• Requires ventilatory support, including home ventilator
• Surgical procedure or botulinum toxin injection from 6 months prior to the study and during the time of the study
• Patient's medical condition does not permit safe travel.

• Previously received any form of cellular therapy.

  • Autologous umbilical cord blood unit has any of the following:
  • Total nuclear cell dose < 2 x 10e7 cells/kilogram
  • Positive maternal infectious disease markers (except CMV)
  • Evidence of infectious contamination of the cord blood unit
• Lack of a test sample to confirm identity
• Evidence of a genetic disease
• Unable to obtain parental consent.

Contacts and Locations

Contacts

Contact: Omer Bar-Yosef, MD.PHD; 972-35302895; Omer.BarYosef@sheba.health.gov.il

Sponsors and Collaborators

Sheba Medical Center

Investigators

• Study Director: Omer Bar-Yosef, MD.PHD; Sheba Medical Center

More Information

Publications:

Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N, Dan B, Jacobsson B, Damiano D; Executive Committee for the Definition of Cerebral Palsy. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005 Aug;47(8):571-6. Review.

Colver A, Fairhurst C, Pharoah PO. Cerebral palsy. Lancet. 2014 Apr 5;383(9924):1240-9. doi: 10.1016/S0140-6736(13)61835-8. Epub 2013 Nov 20. Review.

Clark SL, Hankins GD. Temporal and demographic trends in cerebral palsy--fact and fiction. Am J Obstet Gynecol. 2003 Mar;188(3):628-33. Review.

• Responsible Party: Dr. Omer Bar-Yosef, M.D.-Ph.D. Peadiatric Neurology and Child Development. Deputy Director The Edmond and Lily Safra Children's Hospital, Sheba Medical Center
• ClinicalTrials.gov Identifier: NCT04243408
• Other Study ID Numbers: SHEBA-18-5102-OBY-CTIL
• First Posted: January 28, 2020
• Last Update Posted: January 31, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: data set of the baseline of the children, the quantity of cord blood transfusion they received and the clinical followup information.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: within 2 years from the end of data collection

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Dr. Omer Bar-Yosef, Sheba Medical Center:

cerebral palsy, autologous umbilical cord blood

Additional relevant MeSH terms:

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