scholarly journals 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

2019 ◽  
Vol 30 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Nazi Derakhshanrad ◽  
Hooshang Saberi ◽  
Mir Saeed Yekaninejad ◽  
Mohammad Taghi Joghataei
Keyword(s):  
Clinical Trial ◽  
Spinal Cord ◽  
Placebo Group ◽  
Spinal Cord Injuries ◽  
Functional Improvement ◽  
Granulocyte Colony Stimulating Factor ◽  
Double Blind ◽  
Cord Injury ◽  
The Mean ◽  
Stimulating Factor

OBJECTIVEGranulocyte-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.METHODSThis 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.RESULTSAmong 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).CONCLUSIONSIncomplete subacute TSCI is associated with significant motor, sensory, and functional improvement after administration of G-CSF.Clinical trial registration no.: IRCT201407177441N3 (www.irct.ir)

scholarly journals Granulocyte-colony stimulating factor administration for neurological improvement in patients with postrehabilitation chronic incomplete traumatic spinal cord injuries: a double-blind randomized controlled clinical trial

2018 ◽  
Vol 29 (1) ◽  
pp. 97-107 ◽  
Author(s):  
Nazi Derakhshanrad ◽  
Hooshang Saberi ◽  
Mir Saeed Yekaninejad ◽  
Mohammad Taghi Joghataei ◽  
Abdolreza Sheikhrezaei
Keyword(s):  
Clinical Trial ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Placebo Group ◽  
Spinal Cord Injuries ◽  
Functional Improvement ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Cord Injury

OBJECTIVEGranulocyte-colony stimulating factor (G-CSF) is a major growth factor for activation and differentiation of granulocyte colonies in the bone marrow. This cytokine has been widely and safely employed in different conditions over many years. The purpose of this study was to investigate the efficacy of G-CSF administration for traumatic spinal cord injury (TSCI).METHODSThis double-blind parallel randomized, placebo-controlled, clinical trial, a phase III study, was performed from June 2013 to June 2016 in the Brain and Spinal Cord Injury Research (BASIR) center at Tehran University of Medical Sciences (TUMS). It included 120 patients with incomplete chronic TSCI, American Spinal Injury Association (ASIA) Impairment Scale (AIS) B, C, or D, of at least 6 months’ duration. Sixty patients were allocated into the treatment group and 60 patients into the control group. All the patients had completed an outpatient rehabilitation program in the postacute period and were in a neurological and functional plateau. Patients were assessed with the ASIA grading system, the Spinal Cord Independence Measure (SCIM-III), and the International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) just before intervention and at 1, 3, and 6 months after 7 subcutaneous administrations of 300 μg/day of G-CSF in the treatment group and placebo in the control group (administered once per day over the course of 1 week). Randomization was performed with randomized block design, and the patients and evaluators were blinded regarding the treatment groups. One patient did not receive the entire allocated intervention and 5 patients were lost to follow-up. Thus data from 114 patients were included in the analysis.RESULTSOne hundred twenty patients were randomized and allocated into the study groups. Among them, 56 patients (93.3%) in the G-CSF group and 58 patients (96.6%) in the placebo group completed the study protocol. After 6 months of follow-up, AIS in the placebo group remained unchanged, whereas in the G-CSF group, 1 patient improved from AIS B to C, and 4 patients improved from AIS C to D. The mean (± SE) improvement in ASIA motor score in the G-CSF group was 5.5 ± 0.62, which was significantly more than in the placebo group (0.77 ± 0.20) (p < 0.001). The mean light touch and pinprick sensory scores, respectively, increased by 6.1 ± 1.1 and 8.7 ± 1.5 in the G-CSF group and by 1.3 ± 0.52 and 0.89 ± 0.44 scores in the placebo group (p < 0.001). Evaluation of functional improvement by the IANR-SCIFRS instrument revealed significantly more improvement in the G-CSF group (3.5 ± 0.37) than in the placebo group (0.41 ± 0.12) (p < 0.001). Also, a significant difference was observed in functional improvement between the 2 groups as measured by SCIM-III instrument (7.5 ± 0.95 vs 2.1 ± 0.51, p < 0.001).CONCLUSIONSAdministration of G-CSF for incomplete chronic spinal cord injuries is associated with significant motor, sensory, and functional improvement.Clinical trial registration no.: IRCT201108297441N1 (www.irct.ir)

Neuroprotective effects of granulocyte colony-stimulating factor and relationship to promotion of angiogenesis after spinal cord injury in rats

2011 ◽  
Vol 15 (4) ◽  
pp. 414-421 ◽  
Author(s):  
Junko Kawabe ◽  
Masao Koda ◽  
Masayuki Hashimoto ◽  
Takayuki Fujiyoshi ◽  
Takeo Furuya ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treated Group ◽  
Control Group ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Neuroprotective Effects ◽  
Cord Injury ◽  
Bone Marrow Derived Cells ◽  
Stimulating Factor ◽  
Angiogenic Cytokines

Object Granulocyte colony-stimulating factor (G-CSF) has neuroprotective effects on the CNS. The authors have previously demonstrated that G-CSF also exerts neuroprotective effects in experimental spinal cord injury (SCI) by enhancing migration of bone marrow–derived cells into the damaged spinal cord, increasing glial differentiation of bone marrow–derived cells, enhancing antiapoptotic effects on both neurons and oligodendrocytes, and by reducing demyelination and expression of inflammatory cytokines. Because the degree of angiogenesis in the subacute phase after SCI correlates with regenerative responses, it is possible that G-CSF's neuroprotective effects after SCI are due to enhancement of angiogenesis. The aim of this study was to assess the effects of G-CSF on the vascular system after SCI. Methods A contusive SCI rat model was used and the animals were randomly allocated to either a G-CSF–treated group or a control group. Integrity of the blood–spinal cord barrier was evaluated by measuring the degree of edema in the cord and the volume of extravasation. For histological evaluation, cryosections were immunostained with anti–von Willebrand factor and the number of vessels was counted to assess revascularization. Real-time reverse transcriptase polymerase chain reaction was performed to assess expression of angiogenic cytokines, and recovery of motor function was assessed with function tests. Results In the G-CSF–treated rats, the total number of vessels with a diameter > 20 μm was significantly larger and expression of angiogenic cytokines was significantly higher than those in the control group. The G-CSF–treated group showed significantly greater recovery of hindlimb function than the control group. Conclusions These results suggest that G-CSF exerts neuroprotective effects via promotion of angiogenesis after SCI.

scholarly journals TASCI—transcutaneous tibial nerve stimulation in patients with acute spinal cord injury to prevent neurogenic detrusor overactivity: protocol for a nationwide, randomised, sham-controlled, double-blind clinical trial

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e039164 ◽  
Author(s):  
Veronika Birkhäuser ◽  
Martina D Liechti ◽  
Collene E Anderson ◽  
Lucas M Bachmann ◽  
Sarah Baumann ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tibial Nerve ◽  
Ethics Committee ◽  
Neurogenic Detrusor Overactivity ◽  
Double Blind ◽  
Tibial Nerve Stimulation ◽  
Double Blind Clinical Trial ◽  
Cord Injury

IntroductionNeurogenic lower urinary tract dysfunction (NLUTD), including neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia, is one of the most frequent and devastating sequelae of spinal cord injury (SCI), as it can lead to urinary incontinence and secondary damage such as renal failure. Transcutaneous tibial nerve stimulation (TTNS) is a promising, non-invasive neuromodulatory intervention that may prevent the emergence of the C-fibre evoked bladder reflexes that are thought to cause NDO. This paper presents the protocol for TTNS in acute SCI (TASCI), which will evaluate the efficacy of TTNS in preventing NDO. Furthermore, TASCI will provide insight into the mechanisms underlying TTNS, and the course of NLUTD development after SCI.Methods and analysisTASCI is a nationwide, randomised, sham-controlled, double-blind clinical trial, conducted at all four SCI centres in Switzerland. The longitudinal design includes a baseline assessment period 5–39 days after acute SCI and follow-up assessments occurring 3, 6 and 12 months after SCI. A planned 114 participants will be randomised into verum or sham TTNS groups (1:1 ratio), stratified on study centre and lower extremity motor score. TTNS is performed for 30 min/day, 5 days/week, for 6–9 weeks starting within 40 days after SCI. The primary outcome is the occurrence of NDO jeopardising the upper urinary tract at 1 year after SCI, assessed by urodynamic investigation. Secondary outcome measures assess bladder and bowel function and symptoms, sexual function, neurological structure and function, functional independence, quality of life, as well as changes in biomarkers in the urine, blood, stool and bladder tissue. Safety of TTNS is the tertiary outcome.Ethics and disseminationTASCI is approved by the Swiss Ethics Committee for Northwest/Central Switzerland, the Swiss Ethics Committee Vaud and the Swiss Ethics Committee Zürich (#2019-00074). Findings will be disseminated through peer-reviewed publications.Trial registration numberNCT03965299.

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