A phase I clinical study of naked DNA expressing two isoforms of hepatocyte growth factor to treat patients with critical limb ischemia.
BACKGROUND
The purpose of the present phase I clinical trial was to evaluate the safety, tolerability, and preliminary efficacy of naked DNA therapy expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in critical limb ischemia (CLI) patients.


METHODS
Twenty-one patients with CLI were consecutively assigned to receive increasing doses (cohort I: 4  mg; cohort II: 8  mg; cohort III: 12  mg; and cohort IV: 16  mg) of pCK-HGF-X7, which was administered into the ischemic calf and/or thigh muscle at days 1 and 15. A safety and tolerability evaluation and measurement of pain severity score using a visual analog scale (VAS), ulcer status, transcutaneous oxygen (TcPO(2) ) and ankle-brachial index (ABI) were performed throughout a 3-month follow-up period.


RESULTS
No serious adverse events were observed in any of the 21 patients for the 3-month follow-up period. A significant reduction in pain was observed in the treated patients, with the mean VAS decreasing from 5.95-1.64 (p  <  0.001). The mean ABI value increased from 0.49-0.63 (p  =  0.026) at 3-month follow-up. The mean TcPO(2) value on the dorsum of the foot, the anterior calf and posterior calf significantly increased from 28.25-39.28  mmHg (p  =  0.012), from 22.00-30.63  mmHg (p  =  0.046) and 32.05-47.19  mmHg (p  =  0.001) at 3-month follow-up, respectively. Wound healing improvement was observed in the six of nine patients that had an ulcer at baseline.


CONCLUSIONS
These results support the performance of a phase II randomized controlled trial with pCK-HGF-X7.
Vascular Surgery Department of Xuan Wu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing, China. guyq66@yahoo.cn
Yongquan
Y
Gu
Jian
J
Zhang
Lianrui
L
Guo
Shijun
S
Cui
Xuefeng
X
Li
Dayou
D
Ding
Jong-Mook
JM
Kim
Seong-Hyun
SH
Ho
Woong
W
Hahn
Sunyoung
S
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055109:Ankle Brachial Index; D001785:Blood Gas Monitoring, Transcutaneous / Q000379:methods; D017719:Diabetic Foot / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000628:therapy; D058729:Peripheral Arterial Disease / Q000628:therapy; D020033:Protein Isoforms / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D014945:Wound Healing; D055815:Young Adult
C066855:HGF protein, human; D020033:Protein Isoforms; D017228:Hepatocyte Growth Factor