title: Phase II clinical trial of CD34+ cell therapy to explore endpoint selection and timing in patients with critical limb ischemia.
abstract: BACKGROUND
  A prior phase I/IIa clinical trial provided evidence for safety, feasibility and potential efficacy of i.m. injection of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34+ cells in patients with critical limb ischemia (CLI).
  
  
  RESULTS
  A phase II trial of CD34+ cell therapy was conducted in patients with CLI to explore endpoint selection and timing. No-option CLI patients (n=11) underwent i.m. transplantation of G-CSF-mobilized CD34+ cells isolated by magnetic sorting. Ischemic rest pain scales improved from week 2 vs. baseline (P<0.05). Skin perfusion pressure (P=0.0175), transcutaneous partial oxygen pressure (P=0.0446) and pain-free walking distance (P=0.0056) improved from week 2, total walking distance from week 8 (P=0.0182) and toe brachial pressure index from week 12 (P=0.0174) vs. baseline. These parameters peaked at week 36 or 52. Rutherford's category improved from week 24 vs. baseline (P=0.0065). CLI-free ratio serially increased and peaked (85.7%) at week 36. Serial change in Rutherford's category correlated with that in Rest Pain Scale (P=0.0374), but not with that in any physiological parameters.
  
  
  CONCLUSIONS
  Ischemic rest pain scales and physiological parameters improved relatively early after cell therapy, then plateaued later accompanied by recovery from the CLI state. Rutherford's category and CLI-free ratio at week 36 or later may be suitable endpoints in cell therapy clinical trials for CLI. Functional parameters should be evaluated independently of such clinical endpoints for ischemia severity. (
  
  
  BACKGROUND
  URL: https://dbcentre3.jmacct.med.or.jp/jmactr/Default.aspx. Unique identifier: JMA-IIA00022)
authors.affiliation: Division of Vascular Regeneration, Unit of Regenerative Medicine, Institute of Biomedical Research and Innovation.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujita
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Nagano
authors.forename: Hisako
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hirami
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kurimoto
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Arakawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Yukikatsu
authors.initials: Y
authors.lastname: Okada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.forename: Emiko
authors.initials: E
authors.lastname: Uno
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukushima
authors.forename: Adel
authors.initials: A
authors.lastname: Nada
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okita
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D064592:Autografts; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D005260:Female; D006801:Humans; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy; D035002:Lower Extremity / Q000098:blood supply / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000503:physiopathology*; D059408:Pain Management; D033581:Stem Cell Transplantation; D013234:Stem Cells
chemical_list: D018952:Antigens, CD34