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

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>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 &lt; 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 &lt; 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 &lt; 0.001).</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>Incomplete subacute TSCI is associated with significant motor, sensory, and functional improvement after administration of G-CSF.</jats:p><jats:p>Clinical trial registration no.: IRCT201407177441N3 (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.irct.ir">www.irct.ir</jats:ext-link>)</jats:p></jats:sec>

Evidence of treating spasticity before it develops: a systematic review of spasticity outcomes in acute spinal cord injury interventional trials

“… 29 , 34 The remainder of the studies evaluated spasticity as a secondary outcome, except for one which measured spasticity as a possible adverse event. 30 Sample size calculations were described in three studies, in which one used a secondary outcome measure to determine the sample size. 30 Three of the studies justified the lack of a sample size calculation because they were pilot trials, while two did not provide any information on sample size.…”

“… 30 Sample size calculations were described in three studies, in which one used a secondary outcome measure to determine the sample size. 30 Three of the studies justified the lack of a sample size calculation because they were pilot trials, while two did not provide any information on sample size. Seven of the eight trials included people with SCI that already had spasticity as baseline, and one of the studies did not provide information on baseline spasticity.…”

“…Derakhshanrad et al 30 performed an RCT in 54 subjects testing granulocyte-colony-stimulating factor (G-CSF) to detect ISNSCI score changes between groups. Changes in the motor scores were significantly greater in the G-CSF group (14.9 ± 2.6) compared with the placebo group (1.4 ± 034, p < 0.001).…”

Clinical Neurorestorative Therapeutic Guidelines for Spinal Cord Injury (IANR/CANR version 2019)

“…Treatment with acidic fibroblast growth factor and granulocyte colony-stimulating factor may be beneficial for chronic SCI, but these therapies need higher level evidence to be confirmed [[143], [144], [145]].…”

2018 Yearbook of Neurorestoratology

“…Granulocyte-colony stimulating factor (GCSF) had some benefits in cases of incomplete subacute and chronic SCI in some studies of double-blind randomized controlled clinical trials [55,56].…”