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.