The "Reducing Inflammation for Greater Health Trial (RIGHT)" Study-Concept, Rationale, and Design.

The Reducing Inflammation for Greater Health Trial's (RIGHT) study is a single-center, randomized, double-blind, placebo-controlled trial designed to test whether clazkizumab, an interleukin-6 (IL-6) inhibitor, can improve or slow decline in physical, cognitive, and vascular function in older adults, when compared to a placebo. The trial will enroll participants meeting the following inclusion criteria: (1) ≥ 70 years of age, (2) with low to moderate physical function, defined as self-reported difficulty walking 1/4 mile or climbing a flight of stairs, but able to walk 400 m at baseline exam, (3) usual walking speed between ≥ 0.44 and < 1.0 m/s on a 4-m walk or a body mass index of ≥ 28 kg/m2, (4) average IL-6 level between 2.0 and 30 pg/mL on two tests, and (5) no active infection, cancer, or other serious health conditions. Clazakizumab, a monoclonal antibody targeting IL-6, 5 mg via subcutaneous injection every 4 weeks for 24 weeks compared to a placebo. The primary outcome will be walking speed over 400 m. Secondary outcomes include other measures of physical function (short physical performance battery, oxygen consumption with walking on a treadmill, fatigability), cognitive function, vascular stiffness and endothelial function, IL-6 and C-reactive protein levels, other markers of inflammation, safety, and tolerability. Findings will evaluate acceptability, safety and 6-months change in mobility and other outcomes. The study was approved by the IRB and is registered with ClinicalTrials.gov (NCT05727384). The RIGHT study will inform the geroscience hypothesis that modifying aging itself will lead to improvement in multiple aspects of health.