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

Phase 1

Completed

• Conditions: Neurodegeneration; Peripheral Blood Mononuclear Cells; Cerebral Palsy; G-CSF
• Interventions: Biological: Peripheral blood mononuclear cells (mPBMC); Drug: G-CSF; Drug: Placebo

• Registration Number: NCT02983708
• Lead Sponsor: Hanyang University Seoul Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-08
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Status Verified: 2016-12
• Study First Submitted: 2016-12-02
• Study First Submitted QC: 2016-12-02
• Last Update Submitted: 2016-12-05
• Study First Posted: 2016-12-06
• Last Update Posted: 2016-12-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 57

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
mPBMC group	Peripheral blood mononuclear cells (mPBMC)	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.
mPBMC group	G-CSF	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.
Placebo group	G-CSF	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.
Placebo group	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Overall improvement as a score changes in GMFM > 4 points	6 months