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

Study Overview
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Brief Summary
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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

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

Conditions
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Cerebral Palsy

Intervention / Treatment
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* Other: Autologous umbilical cord blood transfusion
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1<br> | Other: Autologous umbilical cord blood transfusion<br>* single dose of an autologous umbilical cord blood transfusion<br>|
| Placebo Comparator: group 2<br> | Other: placebo<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor developmental improvement | 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 . | 6 months | 
| Motor developmental improvement | Peabody developmental motor scales-second edition (PDMS-2). All score are normalized with mean 100 and STD 10. High score is better | 6 months | 
| Functional assessment | Pediatric Evaluation of Disability Evaluation . Score 0-100 higher score better functionality Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional assessment | 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 . | 6 months | 
| Functional assessment | 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 . | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cerebral palsy, autologous umbilical cord blood