Subcutaneous granulocyte colony-stimulating factor administration for subacute traumatic spinal cord injuries, report of neurological and functional outcomes: a double-blind randomized controlled clinical trial

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OBJECTIVE

Granulocyte-colony stimulating factor (G-CSF) is a major cytokine that has already been clinically verified for chronic traumatic spinal cord injuries (TSCIs). In this study, the authors set out to determine the safety and efficacy of G-CSF administration for neurological and functional improvement in subacute, incomplete TSCI.

METHODS

This phase II/III, prospective, double-blind, placebo-controlled, parallel randomized clinical trial was performed in 60 eligible patients (30 treatment, 30 placebo). Patients with incomplete subacute TSCIs with American Spinal Injury Association Impairment Scale (AIS) grades B, C, and D were enrolled. Patients were assessed using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) scale, Spinal Cord Independence Measure (SCIM-III) and International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), just before intervention and at 1, 3, and 6 months, after 7 daily subcutaneous administrations of 300 μg/day of G-CSF in the treatment group and placebo in the control group.

RESULTS

Among 60 participants, 28 patients (93.3%) in the G-CSF group and 26 patients (86.6%) in the placebo group completed the study protocol. After 6 months of follow-up, the AIS grade remained unchanged in the placebo group, while in the G-CSF group 5 patients (45.5%) improved from AIS grade B to C, 5 (45.5%) improved from AIS grade C to grade D, and 1 patient (16.7%) improved from AIS grade D to E. The mean ± SEM change in ISNCSCI motor score in the G-CSF group was 14.9 ± 2.6 points, which was significantly greater than in the placebo group (1.4 ± 0.34 points, p < 0.001). The mean ± SEM light-touch and pinprick sensory scores improved by 8.8 ± 1.9 and 10.7 ± 2.6 points in the G-CSF group, while those in the placebo group improved by 2.5 ± 0.60 and 1.2 ± 0.40 points, (p = 0.005 and 0.002, respectively). Evaluation of functional improvement according to the IANR-SCIFRS instrument revealed significantly more functional improvement in the G-CSF group (10.3 ± 1.3 points than in the placebo group (3.0 ± 0.81 points; p < 0.001). A significant difference was also observed between the 2 groups as measured by the SCIM-III instrument (29.6 ± 4.1 vs 10.3 ± 2.2, p < 0.001).

CONCLUSIONS

Incomplete subacute TSCI is associated with significant motor, sensory, and functional improvement after administration of G-CSF.

Clinical trial registration no.: IRCT201407177441N3 (www.irct.ir)

ABBREVIATIONS AIS = ASIA Impairment Scale; ASIA = American Spinal Injury Association; BASIR = Brain and Spinal cord Injury Research; CONSORT = Consolidated Standards of Reporting Trials; CBC = complete blood count; G-CSF = granulocyte colony-stimulating factor; IANR-SCIFRS = International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale; ISNCSCI = International Standards for Neurological Classification of Spinal Cord Injury; MAS = Modified Ashworth Scale; MPSS = methylprednisolone sodium succinate; SCIM-III = Spinal Cord Independence Measure version III; TSCI = traumatic spinal cord injury; TUMS = Tehran University of Medical Sciences; VAS = visual analog scale; WBC = white blood cell.

Article Information

Correspondence Hooshang Saberi: Brain and Spinal cord Injury Research Center (BASIR), Neuroscience Institute, Tehran, Iran. hgsaberi@yahoo.com.

INCLUDE WHEN CITING Published online October 12, 2018; DOI: 10.3171/2018.6.SPINE18209.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    CONSORT flow diagram for trial profile.

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    Comparison of ISNCSCI scores. A: ISNCSCI motor scores. There was no significant difference between the groups before treatment (p = 0.645); statistical significance was observed 6 months after treatment (p < 0.001). B: ISNCSCI light-touch scores. There was no significant difference between the groups before treatment (p = 0.651); statistical significance was observed 6 months after treatment (p = 0.002). C: ISNCSCI pinprick scores of the 2 groups. There was no significant difference between the groups before treatment (p = 0.267); statistical significance was observed 6 months after treatment (p < 0.001). Values are means with SEM denoted by the error bars.

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    A: Percentage of AIS changes at final assessment in the G-CSF group. There were no significant changes in AIS grade in the placebo group. B: Comparison of the SCIM scores. No significant difference was noted before treatment (p = 0.136); statistical significance was observed 6 months after treatment (p < 0.001). C: Comparison of the IANR-SCIFRS (FRS) scores. No significant difference before treatment (p = 0.219); statistical significance was observed 6 months after treatment (p < 0.001). Values in B and C are means with SEM denoted by the error bars.

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    Comparison of functional status at 6 months. A: SCIM score; all changes were statistically significant (p < 0.05) except for bathing lower body, use of toilet, bed-wheelchair transfer, and ground-wheelchair transfer. B: IANR-SCIFRS; all changes were statistically significant (p < 0.05) except for bathing, sweating, and skin condition.

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    Comparison of neurological (based on ISNCSCI) and functional (based on SCIM-III and FRS) score changes in subacute (this study) versus chronic (our previous study7) TSCIs treated with G-CSF.

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