Neuroregenerative Potential of Intravenous G-CSF and Autologous Peripheral Blood Stem Cells

Study Overview
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Brief Summary
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The current study describes a randomized, double-blind, cross-over study of intravenous G-CSF followed by infusion with autologous mobilized peripheral blood mononuclear cells (mPBMCs) in children with cerebral palsy (CP) to determine the safety and feasibility of the procedure, as well as the potential efficacy for improving neurological impairment.

Detailed Description
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We hypothesized that mobilized peripheral blood mononuclear cells (mPBMCs) would be a better source of cell therapy for children with CP, if these cells had a similar neuroregenerative potential to bone marrow/cord blood mononuclear cells (MNCs). Multipotent precursor cells exist in peripheral blood, and a fraction of elutriated blood cells from normal individuals contains MNCs that have the potential to be MSCs. There are several advantages to using mPBMCs for cell therapy in children with CP: the G-CSF that is used to mPBMCs has neuroregenerative potential; the collection and fractionation of stem cells can be repeated; and, the therapy is suitable for most children with CP.

Official Title
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Neuroregenerative Potential of Intravenous G-CSF and Autologous Peripheral Blood Stem Cells in Children With Cerebral Palsy: a Randomized, Double-blind Cross-over Study

Conditions
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Neurodegeneration, G-CSF, Peripheral Blood Mononuclear Cells, Cerebral Palsy

Intervention / Treatment
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* Biological: Peripheral blood mononuclear cells (mPBMC)
* Drug: G-CSF
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non severe type of cerebral palsy Evidences of abnormal MRI findings such as periventricular leukomalacia Collected mobilized peripheral blood mononuclear cell counts > 1×10^8/kg or CD34+ cell counts > 1×10^6/kg Consent form Exclusion Criteria: Previous trials of autologous cord blood infusion or erythropoietin/G-CSF Chromosomal abnormalities

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 10 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mPBMC group<br>G-CSF would be administered for 5 days and then mobilized peripheral blood mononuclear cells (mPBMCs) would be collected in all included patients. One month after cryopreservation of the mPBMCs (M1), patients will be randomized to receive either mPBMCs or placebo. Six months after randomization (M7), cross-over infusion of mPBMCs or placebo will be performed and the patients are observed for another 6 months. mPBMCs group would be included all patients who received mPBMCs at M1 or M7. | Biological: Peripheral blood mononuclear cells (mPBMC)<br> <br> Drug: G-CSF<br> <br> |
| Placebo Comparator: Placebo group<br>G-CSF would be administered for 5 days and then mobilized peripheral blood mononuclear cells (mPBMCs) would be collected in all included patients. One month after cryopreservation of the mPBMCs (M1), patients will be randomized to receive either mPBMCs or placebo. Six months after randomization (M7), cross-over infusion of mPBMCs or placebo will be performed and the patients are observed for another 6 months. Placebo group would be included all patients who received placebo at M1 or M7. | Drug: G-CSF<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall improvement as a score changes in GMFM > 4 points |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuroregeneration, G-CSF, Peripheral blood mononuclear cells, Cerebral palsy