Randomized trial of granulocyte colony-stimulating factor for spinal cord injury

Masao Koda, Hideki Hanaoka, Yasuhisa Fujii, Michiko Hanawa, Yohei Kawasaki, Yoshihito Ozawa, Tadami Fujiwara, Takeo Furuya, Yasushi Ijima, Junya Saito, Mitsuhiro Kitamura, Takuya Miyamoto, Seiji Ohtori, Yukei Matsumoto, Tetsuya Abe, Hiroshi Takahashi, Kei Watanabe, Toru Hirano, Masayuki Ohashi, Hirokazu ShojiTatsuki Mizouchi, Norio Kawahara, Masahito Kawaguchi, Yugo Orita, Takeshi Sasamoto, Masahito Yoshioka, Masafumi Fujii, Katsutaka Yonezawa, Daisuke Soma, Hiroshi Taneichi, Daisaku Takeuchi, Satoshi Inami, Hiroshi Moridaira, Haruki Ueda, Futoshi Asano, Yosuke Shibao, Ikuo Aita, Yosuke Takeuchi, Masaya Mimura, Jun Shimbo, Yukio Someya, Sumio Ikenoue, Hiroaki Sameda, Kan Takase, Yoshikazu Ikeda, Fumitake Nakajima, Mitsuhiro Hashimoto, Fumio Hasue, Takayuki Fujiyoshi, Koshiro Kamiya, Masahiko Watanabe, Hiroyuki Katoh, Yukihiro Matsuyama, Tomohiko Hasegawa, Go Yoshida, Hideyuki Arima, Yu Yamato, Shin Oe, Daisuke Togawa, Sho Kobayashi, Koji Akeda, Eiji Kawamoto, Hiroshi Imai, Toshihiko Sakakibara, Akihiro Sudo, Yasuo Ito, Takeshi Kikuchi, Tomoyuki Takigawa, Takuya Morita, Nobuhiro Tanaka, Kazuyoshi Nakanishi, Naosuke Kamei, Shinji Kotaka, Hideo Baba, Tsuyoshi Okudaira, Hiroaki Konishi, Takayuki Yamaguchi, Keigo Ito, Yoshito Katayama, Taro Matsumoto, Tomohiro Matsumoto, Haruo Kanno, Toshimi Aizawa, Ko Hashimoto, Toshimitsu Eto, Takehiro Sugaya, Michiharu Matsuda, Kazunari Fushimi, Satoshi Nozawa, Chizuo Iwai, Toshihiko Taguchi, Tsukasa Kanchiku, Hidenori Suzuki, Norihiro Nishida, Masahiro Funaba, Takashi Sakai, Yasuaki Imajo, Masashi Yamazaki

Research output: Contribution to journalArticlepeer-review

Abstract

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.

Original languageEnglish
Pages (from-to)789-799
Number of pages11
JournalBrain : a journal of neurology
Volume144
Issue number3
DOIs
Publication statusPublished - 2021 Apr 12
Externally publishedYes

Keywords

  • G-CSF
  • clinical trial
  • neuroprotection
  • spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology

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