TY - JOUR
T1 - Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia
AU - Kumagai, Motoyuki
AU - Marui, Akira
AU - Tabata, Yasuhiko
AU - Takeda, Takahide
AU - Yamamoto, Masaya
AU - Yonezawa, Atsushi
AU - Tanaka, Shiro
AU - Yanagi, Shigeki
AU - Ito-Ihara, Toshiko
AU - Ikeda, Takafumi
AU - Murayama, Toshinori
AU - Teramukai, Satoshi
AU - Katsura, Toshiya
AU - Matsubara, Kazuo
AU - Kawakami, Koji
AU - Yokode, Masayuki
AU - Shimizu, Akira
AU - Sakata, Ryuzo
N1 - Publisher Copyright:
© 2015, Springer Japan.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I–IIa study that analyzed 10 CLI patients following a 200-μg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger’s disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI.
AB - As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I–IIa study that analyzed 10 CLI patients following a 200-μg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger’s disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI.
KW - Angiogenesis
KW - Basic fibroblast growth factor
KW - Critical limb ischemia
KW - Drug delivery system
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U2 - 10.1007/s00380-015-0677-x
DO - 10.1007/s00380-015-0677-x
M3 - Article
C2 - 25861983
AN - SCOPUS:84927553862
SN - 0910-8327
VL - 31
SP - 713
EP - 721
JO - Heart and Vessels
JF - Heart and Vessels
IS - 5
ER -