Repurposing colchicine for reduction of residual inflammatory risk in type 1 diabetes: Design and rationale of the REC1TE trial

AIMS: Compared to people without diabetes, individuals with type 1 diabetes have a several-fold increased risk of cardiovascular (CV) morbidity and mortality despite guideline-recommended management of traditional risk factors; so-called residual CV risk. Systemic low-grade inflammation has emerged as an independent risk factor for CV events with residual inflammatory risk referring to the increased risk conferred by inflammation when all other risk factors are well-treated. Several clinical trials in individuals without type 1 diabetes have demonstrated improved CV outcomes when targeting residual inflammatory risk with anti-inflammatory therapies, of which especially low-dose colchicine has shown promise and has been approved by the FDA for atherosclerotic CV disease (CVD) prevention.

MATERIALS AND METHODS: This trial is an investigator-initiated, randomised, double-blind, placebo-controlled phase 2b trial evaluating low-dose colchicine (0.5 mg/day) in individuals with type 1 diabetes, established or high risk of atherosclerotic CVD and residual inflammatory risk (defined as two consecutive measurements of high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L). A total of 102 participants have been included in the trial and randomly assigned to colchicine or placebo (1:1) for up to 52 weeks in addition to standard of care. The primary endpoint is the difference in hsCRP at week 26. Recruitment began August 2023 and last patient last visit is expected in February 2026.

RESULTS AND CONCLUSIONS: Here, we present the protocol for a study designed to evaluate the efficacy of low-dose colchicine on residual inflammatory risk in individuals with type 1 diabetes.