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Background <p>Coronary 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.</p> Methods <p>This is a single-centre, randomised, double-blind, placebo-controlled, superiority trial at Aarhus University Hospital, Denmark. We have randomised 187 patients aged ≥ 65&#xa0;years with CAD (prior coronary artery revascularisation or myocardial infarction ≥ 3&#xa0;months prior to screening) and preserved left ventricular ejection fraction (&gt; 40%) in a 1:1 ratio to receive either 24&#xa0;mg/day spermidine or placebo for 48&#xa0;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⁻<sup>1</sup>·min⁻<sup>1</sup>) by cardiopulmonary exercise testing, (3) appendicular lean mass (g) by dual-energy X-ray absorptiometry, and (4) high-sensitivity C-reactive protein (mg/L). Secondary outcomes include 24-h ambulatory blood pressure, arterial stiffness, physical performance, muscle strength, daily physical activity, quality of life, cognitive function, dietary spermidine intake, and spermidine levels in plasma and skeletal muscle. Safety monitoring includes laboratory testing, telephone interviews and adverse event recording.</p> Discussion <p>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.</p> Trial registration <p>ClinicalTrials.gov identifier NCT06186102 (first posted 12 June 2023). Participant enrolment began on 4 January 2024, and trial completion is anticipated in August 2026.</p>

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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

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  • 发表日期：

    2025年10月30日

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  • Christian Velling Thorup,
  • Chris Nørgaard Agerbo Jeppesen,
  • Thomas Hvid Jensen,
  • Andreas Bugge Tinggaard,
  • Christian Lodberg Hvas,
  • Charlotte Lock Rud,
  • Maria Kreiberg Skou,
  • Janne Kaergaard Mortensen,
  • Fulvio Reggiori,
  • Jörn Dengjel,
  • Jakob Wang,
  • Jean Farup,
  • Niels Jessen,
  • Won Yong Kim,
  • Henrik Wiggers

摘要

Background

Coronary 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.

Methods

This 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⁻1·min⁻1) by cardiopulmonary exercise testing, (3) appendicular lean mass (g) by dual-energy X-ray absorptiometry, and (4) high-sensitivity C-reactive protein (mg/L). Secondary outcomes include 24-h ambulatory blood pressure, arterial stiffness, physical performance, muscle strength, daily physical activity, quality of life, cognitive function, dietary spermidine intake, and spermidine levels in plasma and skeletal muscle. Safety monitoring includes laboratory testing, telephone interviews and adverse event recording.

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 registration

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