Manini Todd M, Anton Stephen D, Beavers Daniel P, Cauley Jane A, Espeland Mark A, Fielding Roger A, Kritchevsky Stephen B, Leeuwenburgh Christiaan, Lewis Kristina H, Liu Christine, McDermott Mary M, Miller Michael E, Tracy Russell P, Walston Jeremy D, Radziszewska Barbara, Lu Jane, Stowe Cindy, Wu Samuel, Newman Anne B, Ambrosius Walter T, Pahor Marco
Department of Aging and Geriatric Research, University of Florida, Gainesville, Florida.
Department of Biostatistical Sciences, School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
J Am Geriatr Soc. 2017 Sep;65(9):1961-1968. doi: 10.1111/jgs.14965. Epub 2017 Jul 22.
To test two interventions to reduce interleukin (IL)-6 levels, an indicator of low-grade chronic inflammation and an independent risk factor for impaired mobility and slow walking speed in older adults.
The ENabling Reduction of low-Grade Inflammation in SEniors (ENRGISE) Pilot Study was a multicenter, double-blind, placebo-controlled randomized pilot trial of two interventions to reduce IL-6 levels.
Five university-based research centers.
Target enrollment was 300 men and women aged 70 and older with an average plasma IL-6 level between 2.5 and 30 pg/mL measured twice at least 1 week apart. Participants had low to moderate physical function, defined as self-reported difficulty walking one-quarter of a mile or climbing a flight of stairs and usual walk speed of less than 1 m/s on a 4-m usual-pace walk.
Participants were randomized to losartan, omega-3 fish oil (ω-3), combined losartan and ω-3, or placebo. Randomization was stratified depending on eligibility for each group. A titration schedule was implemented to reach a dose that was safe and effective for IL-6 reduction. Maximal doses were 100 mg/d for losartan and 2.8 g/d for ω-3.
IL-6, walking speed over 400 m, physical function (Short Physical Performance Battery), other inflammatory markers, safety, tolerability, frailty domains, and maximal leg strength were measured.
Results from the ENRGISE Pilot Study will provide recruitment yields, feasibility, medication tolerance and adherence, and preliminary data to help justify a sample size for a more definitive randomized trial.
The ENRGISE Pilot Study will inform a larger subsequent trial that is expected to have important clinical and public health implications for the growing population of older adults with low-grade chronic inflammation and mobility limitations.
测试两种降低白细胞介素（IL）-6水平的干预措施，IL-6是低度慢性炎症的指标，也是老年人行动能力受损和步行速度缓慢的独立危险因素。
老年人低度炎症减少促进（ENRGISE）试点研究是一项多中心、双盲、安慰剂对照的随机试点试验，旨在测试两种降低IL-6水平的干预措施。
五个大学研究中心。
目标招募300名70岁及以上的男性和女性，其血浆IL-6平均水平在2.5至30 pg/mL之间，至少间隔1周测量两次。参与者的身体功能为低到中度，定义为自我报告行走四分之一英里或爬一段楼梯有困难，在4米的常规步速行走中，平常步行速度小于1米/秒。
参与者被随机分为接受氯沙坦、ω-3鱼油（ω-3）、氯沙坦与ω-3联合用药或安慰剂治疗。随机分组根据每组的资格进行分层。实施了滴定方案以达到对降低IL-6安全有效的剂量。氯沙坦的最大剂量为100毫克/天，ω-3为2.8克/天。
测量IL-6、400米步行速度、身体功能（简短身体性能量表）、其他炎症标志物、安全性、耐受性、衰弱领域和最大腿部力量。
ENRGISE试点研究的结果将提供招募成功率、可行性、药物耐受性和依从性，以及初步数据，以帮助确定更明确的随机试验的样本量。
ENRGISE试点研究将为后续更大规模的试验提供信息，预计该试验对越来越多患有低度慢性炎症和行动能力受限的老年人具有重要的临床和公共卫生意义。
