Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy.
Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy.
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DOI：
10.1002/acn3.186
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发表时间：
2015-05
影响因子：
5.3
通讯作者：
Vinik, Aaron
中科院分区：
文献类型：
--
作者：
Kessler, John A.;Smith, A. Gordon;Cha, Bong-Soo;Choi, Sung Hee;Wymer, James;Shaibani, Aziz;Ajroud-Driss, Senda;Vinik, Aaron
目的：评价含有两种人肝细胞生长因子亚型的质粒(VM202)肌肉注射治疗痛性糖尿病神经病变的安全性和有效性。在一项双盲、安慰剂对照研究中，患者被随机分为每条腿注射8或16毫克VM202或安慰剂。在第0天和第14天分别给予不同的剂量。预期的主要结果是通过7天的疼痛日记测量的平均疼痛评分的变化。次要结果包括应答者分析、生活质量和疼痛测量，以及表皮内神经纤维密度。没有可归因于VM202的重大不良事件。84名患者完成了这项研究。在所有疗效测量中，每条腿接受8毫克VM202的患者改善最多，包括在3个月时平均疼痛评分显著降低(P=0.03)，在6个月和9个月时疼痛持续但在统计上没有显著降低。在这些患者中，48.4%的患者经历了≥50%的疼痛减轻，而安慰剂患者的这一比例为17.6%。糖尿病周围神经病变患者的简明疼痛清单和密歇根神经病变筛查工具的问卷部分也有显著改善。未服用普瑞巴林或加巴喷丁的患者疼痛减轻幅度最大。VM202是安全、耐受性良好和有效的，表明非病毒基因治疗方法治疗疼痛的糖尿病神经病变的可行性。两天的治疗足以缓解症状，并改善3个月的生活质量。VM202可能对没有服用加巴喷丁或普瑞巴林的患者特别有益。
To evaluate the safety and efficacy of a plasmid (VM202) containing two human hepatocyte growth factor isoforms given by intramuscular injections in patients with painful diabetic neuropathy. In a double-blind, placebo-controlled study, patients were randomized to receive injections of 8 or 16 mg VM202 per leg or placebo. Divided doses were administered on Day 0 and Day 14. The prospective primary outcome was change in the mean pain score measured by a 7 day pain diary. Secondary outcomes included a responder analysis, quality of life and pain measures, and intraepidermal nerve fiber density. There were no significant adverse events attributable to VM202. Eighty-four patients completed the study. Patients receiving 8 mg VM202 per leg improved the most in all efficacy measures including a significant (P = 0.03) reduction at 3 months in the mean pain score and continued but not statistically significant reductions in pain at 6 and 9 months. Of these patients, 48.4% experienced a ≥50% reduction in pain compared to 17.6% of placebo patients. There were also significant improvements in the brief pain inventory for patients with diabetic peripheral neuropathy and the questionnaire portion of the Michigan Neuropathy Screening Instrument. Patients not on pregabalin or gabapentin had the largest reductions in pain. VM202 was safe, well tolerated and effective indicating the feasibility of a nonviral gene therapy approach to painful diabetic neuropathy. Two days of treatment were sufficient to provide symptomatic relief with improvement in quality of life for 3 months. VM202 may be particularly beneficial for patients not taking gabapentin or pregabalin.
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影响因子：
1.7
作者：
Hashimoto, N;Yamanaka, H;Noguchi, K
通讯作者：
Noguchi, K
影响因子：
5.3
作者：
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影响因子：
12.4
作者：
Ajroud-Driss, Senda;Christiansen, Mark;Kessler, John A.
通讯作者：
Kessler, John A.