Phase II trial of intravenous low-dose granulocyte colony-stimulating factor in acute ischemic stroke

Atsushi Mizuma, Toru Yamashita, Syoichiro Kono, Taira Nakayama, Yasuhiko Baba, Shinji Ito, Kunihiko Asakura, Yoshiki Niimi, Takashi Asahi, Kazuya Kanemaru, Tatsuro Mutoh, Satoshi Kuroda, Hiroyuki Kinouchi, Koji Abe, Shunya Takizawa

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1451-1457
Number of pages7
JournalJournal of Stroke and Cerebrovascular Diseases
Volume25
Issue number6
DOIs
Publication statusPublished - 01-06-2016

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Granulocyte Colony-Stimulating Factor
Stroke
Placebos
National Institutes of Health (U.S.)
Tissue Plasminogen Activator
Sample Size
Leukocytes
Magnetic Resonance Imaging
Safety
Control Groups

All Science Journal Classification (ASJC) codes

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Mizuma, Atsushi ; Yamashita, Toru ; Kono, Syoichiro ; Nakayama, Taira ; Baba, Yasuhiko ; Ito, Shinji ; Asakura, Kunihiko ; Niimi, Yoshiki ; Asahi, Takashi ; Kanemaru, Kazuya ; Mutoh, Tatsuro ; Kuroda, Satoshi ; Kinouchi, Hiroyuki ; Abe, Koji ; Takizawa, Shunya. / Phase II trial of intravenous low-dose granulocyte colony-stimulating factor in acute ischemic stroke. In: Journal of Stroke and Cerebrovascular Diseases. 2016 ; Vol. 25, No. 6. pp. 1451-1457.
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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.",
author = "Atsushi Mizuma and Toru Yamashita and Syoichiro Kono and Taira Nakayama and Yasuhiko Baba and Shinji Ito and Kunihiko Asakura and Yoshiki Niimi and Takashi Asahi and Kazuya Kanemaru and Tatsuro Mutoh and Satoshi Kuroda and Hiroyuki Kinouchi and Koji Abe and Shunya Takizawa",
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Mizuma, A, Yamashita, T, Kono, S, Nakayama, T, Baba, Y, Ito, S, Asakura, K, Niimi, Y, Asahi, T, Kanemaru, K, Mutoh, T, Kuroda, S, Kinouchi, H, Abe, K & Takizawa, S 2016, 'Phase II trial of intravenous low-dose granulocyte colony-stimulating factor in acute ischemic stroke', Journal of Stroke and Cerebrovascular Diseases, vol. 25, no. 6, pp. 1451-1457. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.01.022

Phase II trial of intravenous low-dose granulocyte colony-stimulating factor in acute ischemic stroke. / Mizuma, Atsushi; Yamashita, Toru; Kono, Syoichiro; Nakayama, Taira; Baba, Yasuhiko; Ito, Shinji; Asakura, Kunihiko; Niimi, Yoshiki; Asahi, Takashi; Kanemaru, Kazuya; Mutoh, Tatsuro; Kuroda, Satoshi; Kinouchi, Hiroyuki; Abe, Koji; Takizawa, Shunya.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 25, No. 6, 01.06.2016, p. 1451-1457.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II trial of intravenous low-dose granulocyte colony-stimulating factor in acute ischemic stroke

AU - Mizuma, Atsushi

AU - Yamashita, Toru

AU - Kono, Syoichiro

AU - Nakayama, Taira

AU - Baba, Yasuhiko

AU - Ito, Shinji

AU - Asakura, Kunihiko

AU - Niimi, Yoshiki

AU - Asahi, Takashi

AU - Kanemaru, Kazuya

AU - Mutoh, Tatsuro

AU - Kuroda, Satoshi

AU - Kinouchi, Hiroyuki

AU - Abe, Koji

AU - Takizawa, Shunya

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

AB - 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.

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U2 - 10.1016/j.jstrokecerebrovasdis.2016.01.022

DO - 10.1016/j.jstrokecerebrovasdis.2016.01.022

M3 - Article

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AN - SCOPUS:84962506813

VL - 25

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JO - Journal of Stroke and Cerebrovascular Diseases

JF - Journal of Stroke and Cerebrovascular Diseases

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