title: Phase II Trial of Intravenous Low-Dose Granulocyte Colony-Stimulating Factor in Acute Ischemic Stroke.
abstract: BACKGROUND
  Granulocyte colony-stimulating factor (G-CSF) has shown neuroprotective and neurogenerative activities in experimental studies, and our previous phase I clinical study suggested the safety and potential efficacy of low-dose G-CSF in acute ischemic stroke patients. The present phase II trial is aimed to evaluate the effect of G-CSF administration on neurological function and infarct volume, compared with a placebo group.
  
  
  METHODS
  Forty-nine acute ischemic stroke patients (29 males, 20 females; 71 ± 10 years) within 24 hours after onset were recruited. Eligible patients were randomized 2:2:1 to receive G-CSF 150 µg/body/day, G-CSF 300 µg/body/day, and placebo, respectively. We evaluated clinical outcome in terms of the National Institutes of Health Stroke Scale, the modified Rankin Scale, and the Barthel Index at 90 days after onset, together with changes in infarct volume on magnetic resonance imaging.
  
  
  RESULTS
  We found no serious adverse event, including change in leukocyte levels, which remained below 31,000/µL, at 150 and 300 µg G-CSF/body/day. Clinical outcome scores did not show any significant difference among the 3 groups. Chronological changes in infarct volume also showed no significant difference.
  
  
  CONCLUSIONS
  G-CSF was well-tolerated at 150 and 300 µg/body/day in patients with acute ischemic stroke. However, administration of G-CSF at both 150 and 300 µg/body/day neither contributed to functional recovery nor reduced infarct volume at 3 months after onset, compared with the control group. The apparent lack of effectiveness may have been due to the small sample size. A trial of combination therapy with recombinant tissue plasminogen activator and G-CSF is planned.
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizuma
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Okayama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Okayama, Japan.
authors.forename: Syoichiro
authors.initials: S
authors.lastname: Kono
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Taira
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Baba
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Itoh
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Asakura
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Niimi
authors.affiliation: Department of Neurosurgery, University of Toyama, Toyama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Asahi
authors.affiliation: Department of Neurosurgery, University of Yamanashi, Yamanashi, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kanemaru
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Mutoh
authors.affiliation: Department of Neurosurgery, University of Toyama, Toyama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuroda
authors.affiliation: Department of Neurosurgery, University of Yamanashi, Yamanashi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kinouchi
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Okayama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Japan. Electronic address: shun@is.icc.u-tokai.ac.jp.
authors.forename: Shunya
authors.initials: S
authors.lastname: Takizawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004185:Disability Evaluation; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: Granulocyte colony-stimulating factor; acute stroke; ischemic stroke; neuroprotection; stroke trials