Abstract WP120: Granuloctye-Colony Stimulating Factor in Ischemic Stroke Trial (GIST): A Pilot Study
Introduction: Granulocyte-colony stimulating factor (G-CSF) is upregulated in models of cerebral ischemia. This may promote hematopoietic stem cell (HSC) mediated central nervous system repair. We hypothesize that exogenous G-CSF may promote recovery after acute ischemic stroke. We examined the safety and feasibility of this therapy with a double-blind, randomized pilot study of G-CSF in patients with acute stroke.
Methods: Patients with ischemic stroke and motor deficits greater than 2 on the National Institutes of Health Stroke Scale (NIHSS) were randomized to receive a four-day course of G-CSF (10 μg/kg sc) or matching placebo within ten days of stroke occurrence, followed by a second cycle after six weeks. Primary outcomes were safety measures including recurrent stroke, mortality, toxicity as measured by the NCI Common Toxicity Scale, and worsening of disability as measured by modified Rankin Scale (mRS), Barthel index, NIHSS and Glasgow Outcome Scale (GOS). Testing occurred at 1.5, 3, 6 and 12 months after treatment. MRI, CT perfusion and functional MRI were obtained at 3 months with repeat MRI scan at 12 months, and neuropsychological testing was conducted at 6 and 12 months. Results: Nine patients were randomized; mean pre-treatment NIH Stroke Scale was 8.8. Elevation of circulating leukocytes and CD34+ cells were observed after G-CSF administration compared to placebo. Adverse events including diarrhea, dehydration, bone pain, and asymptomatic leukocytosis were seen more frequently in the G-CSF treated cohort, but there were no recurrent strokes or deaths in either group. Disability did not worsen in any patients, with no significant change in median mRS, NIHSS, GOS or Barthel index between groups at 1.5, 3, 6 or 12 months after treatment. No significant changes in neuropsychological testing or imaging parameters were observed.
Conclusions: G-CSF administration in ischemic stroke patients appears to be safe and feasible, with no increase in mortality or worsening of disability observed in this pilot study. Larger randomized trials would be needed to determine efficacy of this potential novel therapy for stroke recovery.
- © 2012 by American Heart Association, Inc.