Tier 4 — mechanistic

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

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
Trials 2025 26:452

Bibliography

PubMed
PMID 41168834
DOI
10.1186/s13063-025-09176-z
Trial registry
View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.
Funding
The protocol reports support from Sygesikring Danmark, the Danish Diabetes and Endocrine Academy, the Danish Cardiovascular Academy, Steno Diabetes Center Aarhus, and Eva and Frænkels Mindefond. DoNotAge donated the spermidine intervention and matching placebo. The protocol states that funders and the product donor had no role in study design, conduct, analysis or reporting.
Competing interests
The authors reported no conflicts of interest perceived for the study. Henrik Wiggers and Christian Velling Thorup disclosed research grants, and the investigators reported no financial or advisory relationship with DoNotAge.

Study snapshot

DesignRandomized, double-blind, placebo-controlled parallel-group clinical trial protocol
ModelAdults aged 65 years or older with coronary artery disease
Sample187 participants randomized
InterventionSpermidine 24 mg/day versus matching placebo
Duration48 weeks
EndpointsLeft ventricular mass by cardiac MRI; VO2peak; Appendicular lean mass; High-sensitivity C-reactive protein (hs-CRP)

What the study showed, in plain terms

The POLYCAD protocol describes a 48-week randomized, double-blind, placebo-controlled study in 187 adults aged 65 years or older with coronary artery disease. Participants receive 24 mg/day spermidine or matching placebo. DoNotAge donated the intervention and placebo, while the protocol states that the company had no role in study design, conduct, analysis or reporting. The paper describes the study plan and does not provide efficacy results.

Key findings

  • POLYCAD randomized 187 older adults with coronary artery disease to spermidine 24 mg/day or matching placebo for 48 weeks.
  • Co-primary outcomes include left-ventricular mass by cardiac MRI, VO2peak, appendicular lean mass and hs-CRP.
  • DoNotAge donated the spermidine and matching placebo; the protocol states that the donor had no role in study design, conduct, analysis or reporting.
  • This publication is a protocol and contains no intervention-efficacy results.

What this study can and cannot tell us

As a protocol paper, this publication establishes the planned design but cannot show whether spermidine is effective or safe over 48 weeks. Interpretation of efficacy requires the completed randomized trial results, including adherence, attrition, adverse events and prespecified outcome analyses.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology