POLYamine treatment in elderly patients with Coronary Artery Disease (POLYCAD): study protocol for a Danish randomised, double-blind, placebo-controlled trial of spermidine treatment versus placebo.

backgroundCoronary artery disease (CAD) remains a major cause of morbidity and mortality. Caloric restriction promotes cardiovascular health but is difficult to sustain. Spermidine, a naturally occurring polyamine and caloric-restriction mimetic, has been linked to improved longevity in epidemiological studies and shown to enhance autophagy, mitochondrial function, and cardiovascular ageing in preclinical models. This trial will investigate whether high-dose spermidine improves cardiac remodelling, exercise capacity, muscle mass, and systemic inflammation in elderly patients with CAD.

methodsThis is a single-centre, randomised, double-blind, placebo-controlled, superiority trial at Aarhus University Hospital, Denmark. We have randomised 187 patients aged ≥ 65 years with CAD (prior coronary artery revascularisation or myocardial infarction ≥ 3 months prior to screening) and preserved left ventricular ejection fraction (> 40%) in a 1:1 ratio to receive either 24 mg/day spermidine or placebo for 48 weeks. Participants, investigators, outcome assessors, and data analysts will remain blinded until completion of the analysis of all primary endpoints. Analyses will follow the intention-to-treat principle. The trial is powered to detect between-group differences in four co-primary endpoints: (1) left ventricular mass (g) by cardiac magnetic resonance imaging, (2) peak oxygen consumption (mL·kg⁻ DISCUSSION: This is the first trial to investigate the cardiovascular and metabolic benefit from a high-dose spermidine treatment in patients with CAD. The findings will provide important insights into the therapeutic potential of spermidine.

trial registrationClinicalTrials.gov identifier NCT06186102 (first posted 12 June 2023). Participant enrolment began on 4 January 2024, and trial completion is anticipated in August 2026.