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

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

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.

Study Overview

• Status: Completed
• Conditions: Cerebral Palsy; Neurodegeneration; G-CSF; Peripheral Blood Mononuclear Cells
• Intervention / Treatment: Drug: Placebo; Drug: G-CSF; Biological: Peripheral blood mononuclear cells (mPBMC)

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 Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mPBMC group; 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.	Drug: G-CSF; Biological: Peripheral blood mononuclear cells (mPBMC)
Placebo Comparator: Placebo group; 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: Placebo; Drug: G-CSF

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hanyang University Seoul Hospital
• Collaborators: Ministry of Health & Welfare, Korea

Publications and helpful links

General Publications

• Rah WJ, Lee YH, Moon JH, Jun HJ, Kang HR, Koh H, Eom HJ, Lee JY, Lee YJ, Kim JY, Choi YY, Park K, Kim MJ, Kim SH. Neuroregenerative potential of intravenous G-CSF and autologous peripheral blood stem cells in children with cerebral palsy: a randomized, double-blind, cross-over study. J Transl Med. 2017 Jan 21;15(1):16. doi: 10.1186/s12967-017-1120-0.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: December 2, 2016
• First Submitted That Met QC Criteria: December 2, 2016
• First Posted (Estimate): December 6, 2016

Study Record Updates

• Last Update Posted (Estimate): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Cerebral palsy; G-CSF; Neuroregeneration; Peripheral blood mononuclear cells
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Damage, Chronic; Cerebral Palsy; Nerve Degeneration
• Other Study ID Numbers: CP-PB-2011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: We have to get individual permissions to make IPD available to other researchers.