抗疟药氯喹有望用于治疗代谢综合征

休斯顿——抗疟疾/免疫调节药物氯喹可能将增加一项新的用途——治疗代谢综合征患者。

之前华盛顿大学的一项动物研究显示，每日给予氯喹或羟基氯喹治疗可减轻胰岛素抵抗并改善血脂代谢，这很可能是通过激活共济失调毛细血管扩张症基因突变(ATM)实现的(Cell Metab. 2006;4:377-89)。基于动物研究的结果，进行了一系列的大型前瞻性临床试验，评估每日氯喹治疗对于血脂异常和胰岛素抵抗的疗效。

新加坡国立大学的Lawrence Lee博士及其合作者假设，小剂量每周1次氯喹治疗可能对于代谢综合征也有效，并且安全性较每日治疗更佳。这项在健康志愿者中进行的研究拉开了对代谢综合征患者进一步研究的序幕。本次在内分泌学会年会上报告的是氯喹预防流感(CHIP)试验的一项亚研究，在CHIP试验中，1,500例健康志愿者随机接受氯喹或安慰剂治疗，研究结果明确提示氯喹不能预防流感(Lancet Infect. Dis. 2011; 677-83)。

在这项纳入277例健康志愿者的随机双盲试验中，受试者被随机分配到小剂量氯喹组和安慰剂组。氯喹治疗方案包括在最初的7天内给予氯喹每日300 mg，在之后的11周内，给予氯喹每周1次，每次300 mg。

结果显示，经过12周的治疗，氯喹组和安慰剂组的的平均甘油三酯水平分别为77.9 mg/dl和87.7 mg/dl，氯喹组较安慰剂组降低了11%。并且12周时，氯喹组和安慰剂组的总胆固醇:高密度脂蛋白(HDL)比值分别为3.31和3.51，氯喹组较安慰剂组降低了7%。小剂量氯喹治疗12周对HDL、胰岛素水平、血糖或HOMA稳态模型胰岛素敏感性指数均无影响。

研究者总结认为，氯喹治疗可改善健康志愿者的血脂代谢，可能对代谢综合征患者有利。

Lee博士披露无相关利益冲突。CHIP试验由新加坡国立医学研究委员会资助。

爱思唯尔  版权所有

By: BRUCE JANCIN, Clinical Endocrinology News Digital Network

HOUSTON – The antimalarial/immunomodulatory drug chloroquine might take on a new life as a treatment for patients with the metabolic syndrome.

In a randomized, double-blind trial involving 277 healthy Singapore volunteers assigned to low-dose chloroquine or placebo, mean triglyceride levels after 12 weeks were 77.9 mg/dL in the chloroquine group, an 11% reduction compared with the mean 87.7 mg/dL in controls.

Moreover, the total cholesterol–high-density lipoprotein ratio at the 12-week mark was 3.31 mg/dL in the chloroquine group, 7% better than the 3.51 mg/dL in controls, according to Dr. Lawrence Lee of the National University of Singapore.

"This cheap and safe treatment should be investigated further for reducing the risk of cardiovascular disease, especially in high-risk patients, such as those who are obese or diabetic, where the effect could be more clinically significant," he noted at the annual meeting of the Endocrine Society.

Twelve weeks of low-dose chloroquine had no impact on HDL, insulin levels, blood glucose, or the homeostatic model assessment (HOMA) insulin sensitivity index.

The chloroquine regimen consisted of 300 mg/day for the first 7 days followed by 300 mg once weekly for the next 11 weeks.

Previous animal studies by investigators at Washington University at St. Louis showed that daily doses of chloroquine or hydroxychloroquine reduced insulin resistance and improved lipid metabolism, most likely via activation of the ataxia telangiectasis mutated (ATM) gene (Cell Metab. 2006;4:377-89).

This work has led to ongoing large prospective clinical trials of daily chloroquine as a treatment for dyslipidemia and insulin resistance.

Dr. Lee and coworkers hypothesized that low-dose, once-weekly chloroquine could also be effective in metabolic syndrome, and with a more favorable safety profile than that of daily therapy. This study in healthy volunteers was a prelude to further studies in patients with metabolic syndrome.

The current study was actually a substudy of the Chloroquine for Influenza Prevention (CHIP) trial, in which 1,500 healthy volunteers were randomized to chloroquine or placebo, and which established that chloroquine does not prevent influenza (Lancet Infect. Dis. 2011; 677-83).

Dr. Lee reported having no financial conflicts. The CHIP trial was funded by the National Medical Research Council of Singapore.