# The “Reducing Inflammation for Greater Health Trial (RIGHT)” Study—Concept, Rationale, and Design

## TL;DR

This study tests if an IL-6 inhibitor can improve physical, cognitive, and vascular health in older adults.

## Contribution

RIGHT is a novel geroscience trial investigating IL-6 inhibition's impact on age-related health decline.

## Key findings

- RIGHT will assess clazakizumab's effect on walking speed and other age-related outcomes.
- The trial aims to evaluate the safety and tolerability of IL-6 inhibition in older adults.
- Findings may support the geroscience hypothesis that targeting aging improves multiple health aspects.

## Abstract

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.

Key points○Clinical trials studying therapies that can maintain or improve function as people age are essential given the growing population of older adults.○Assessing the effect of the direct interleukin‐6 inhibition on age‐related decline could inform the geroscience hypothesis that modifying aging itself can improve multiple aspects of health.○The RIGHT trial will assess the feasibility, acceptability, safety, and tolerability of clazakizumab compared to placebo and estimate its effect on walking speed.
Why does this paper matter?○This manuscript describes a novel geroscience trial, Reducing Inflammation for Greater Health Trial (RIGHT), a randomized placebo‐controlled trial studying the impact of an interleukin‐6 inhibitor on walking speed and other age‐related outcomes.

Key points○Clinical trials studying therapies that can maintain or improve function as people age are essential given the growing population of older adults.○Assessing the effect of the direct interleukin‐6 inhibition on age‐related decline could inform the geroscience hypothesis that modifying aging itself can improve multiple aspects of health.○The RIGHT trial will assess the feasibility, acceptability, safety, and tolerability of clazakizumab compared to placebo and estimate its effect on walking speed.

Clinical trials studying therapies that can maintain or improve function as people age are essential given the growing population of older adults.

Assessing the effect of the direct interleukin‐6 inhibition on age‐related decline could inform the geroscience hypothesis that modifying aging itself can improve multiple aspects of health.

The RIGHT trial will assess the feasibility, acceptability, safety, and tolerability of clazakizumab compared to placebo and estimate its effect on walking speed.

Why does this paper matter?○This manuscript describes a novel geroscience trial, Reducing Inflammation for Greater Health Trial (RIGHT), a randomized placebo‐controlled trial studying the impact of an interleukin‐6 inhibitor on walking speed and other age‐related outcomes.

This manuscript describes a novel geroscience trial, Reducing Inflammation for Greater Health Trial (RIGHT), a randomized placebo‐controlled trial studying the impact of an interleukin‐6 inhibitor on walking speed and other age‐related outcomes.