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Completed

NCT Number: NCT06186102

Polyamine Treatment in Elderly Patients With Coronary Artery Disease

The present study is testing spermidine treatment in elderly patients with coronary artery disease. The study is a randomized, double-blind, placebo-controlled, two-armed, parallel-group, single centre, clinical study.

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Key information

Conditions

Ischemic Heart Disease Arterial Occlusive Diseases Arteriosclerosis Behavior Behavior, Animal Body Weight Cardiovascular Diseases Cognition Disorder Cognition Disorders Cognitive Dysfunction Cognitive Impairment Coronary Artery Disease Coronary Disease Diabetes Mellitus Diabetes Mellitus, Type 2 Diastolic Dysfunction Dietary Habits Endocrine System Diseases Feeding Behavior Glucose Metabolism Disorders Heart Diseases Hyperinsulinism Hypertension Hypertensive Heart Disease Infarction Inflammation Insulin Resistance Ischemia Mental Disorders Metabolic Diseases Metabolic Syndrome Myocardial Infarction Myocardial Ischemia Necrosis Neurocognitive Disorders Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathologic Processes Pathological Conditions, Signs and Symptoms Quality of Life Signs and Symptoms Vascular Diseases

Age range

65 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Aarhus University Hospital

Aarhus, Jutland, 8200, Denmark

About this study

Life expectancy has increased tremendously over the past century and as populations age, chronic diseases such as cardiovascular disease and diabetes have become more prevalent. Healthy aging is therefore of paramount importance to further promote longevity and quality of life.

In humans, a high concentration of whole-blood spermidine is associated with longevity, and individuals with a high dietary spermidine intake have improved cardiovascular health and less obesity. Spermidine is essentially a polyamine found in all plant-derived foods, particularly in whole grains, soybeans, nuts, and fruit. Its favorable effects may act via several mechanisms. In an experimental model of hypertensive heart disease, spermidine reduced cardiac hypertrophy and improved diastolic and mitochondrial function. Spermidine also induces cytoprotective autophagy in skeletal muscle and alters body fat accumulation by metabolically modulating glucose and lipid metabolism.

The clinical data on spermidine dietary supplementation are scarce. In elderly subjects with cognitive problems, spermidine supplement was well tolerated and had potential blood-pressure-lowering effects. The reported beneficial effects of spermidine raise the question whether elderly patients with cardiovascular disease can benefit from a dietary supplement of this polyamine.

The central hypothesis of the current proposal is that a twelve-month spermidine treatment regimen in elderly patients with cardiovascular disease will yield positive effects on heart and skeletal muscle function, whole body composition and inflammation. The secondary hypotheses are that spermidine reduces blood pressure and has a beneficial impact on cognitive function, daily activity level, quality of life, biomarker risk profile, skeletal muscle cellular metabolism and lastly but not least gut microbiota.

The study design is a randomized, double-blind, placebo-controlled trial to investigate the effects of a 24 mg daily oral spermidine dietary supplement vs. matching placebo in elderly patients with cardiovascular disease. A total of 200 patients will be included and randomized 1:1 to either spermidine 24 mg x 1 daily or matching placebo for one year.

At baseline and after one year of intervention the patients will undergo study procedures. Changes from baseline to follow-up will be compared between the active and placebo treated patient groups.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 65 years
  • Chronic ischemic heart disease (previous revascularization or myocardial infarction)
  • Left ventricular ejection fraction of > 40%

And at least two of the following risk factors:

  • Type 2 diabetes,
  • Obesity (BMI ≥ 30 kg/m2),
  • Hypertension,
  • Previous LVEF < 40%,
  • Left atrial volume index ≥ 30 mL/m2
  • Left ventricular wall thickness ≥ 1.1 cm.

Exclusion criteria

  • Unstable coronary syndrome
  • Significant and severe cardiac valve disease
  • Severe peripheral artery disease
  • Permanent atrial fibrillation
  • Pacemaker treatment
  • Chronic kidney disease with eGFR <45 ml/min/1,73m2
  • Severe comorbidity as judged by the investigator (such as severe pulmonary, neurological, or musculoskeletal disease)
  • Inability to give informed consent.

Exclusion criteria

for MRI:

  • Some metallic implants
  • Claustrophobia

Exclusion criteria

for muscle biopsy:

  • Treatment with either two antiplatelet drugs (aspirin and ADP-receptor antagonists)
  • Anticoagulants (warfarin, NOACs)

Treatment and study plan

Spermidine

Dietary Supplement

Spermidine capsule of 8 mg x 3 capsules daily.

Other names: Polyamine

Placebo

Other

Placebo capsule. 3 capsules daily.

Primary outcomes

  1. Change in left ventricular mass

    Time frame: From randomization (month 0) to 12 months

    Measured with Cardiac Magnetic Resonance Imaging (CMR).

  2. Change in appendicular lean mass and ALM index

    Time frame: From randomization (month 0) to 12 months

    Appendicular lean mass and ALM index (Appendicular lean mass/height^2). Measured by a whole-body dual-energy X ray absorptiometry (DXA) scan.

  3. Change in High-sensitivity C-reactive Protein (hs-CRP)

    Time frame: From randomization (month 0) to 12 months

    Measured from blood samples.

  4. Change in Physical performance, peak oxygen consumption (VO2max)

    Time frame: From randomization (month 0) to 12 months

    Measured by cardiopulmonary exercise capacity (CPET) will be performed using a cycle ergometer test. Peak oxygen uptake measured in ml O2/kg/min.

Secondary outcomes

  1. Muscle strength, Handgrip strength

    Time frame: From randomization (month 0) to 12 months

    Hand-held dynamometer for measuring handgrip strength in kilograms.

  2. Muscle strength, Knee-extension/flexion strength

    Time frame: From randomization (month 0) to 12 months

    Change in knee extension and flexion isokinetic strength (assessed by peak torque, Nm) and isometric strength (assessed by peak torque, Nm).

  3. Physical performance, 6 minute walk test (6MWT)

    Time frame: From randomization (month 0) to 12 months

    Change in walking distance in meters.

  4. Physical performance, 30 seconds sit to stand test

    Time frame: From randomization (month 0) to 12 months

    Change in counts of sit to stand.

  5. The Short Physical Performance Battery

    Time frame: From randomization (month 0) to 12 months

    Changes in points.

  6. Skeletal muscle mass

    Time frame: From randomization (month 0) to 12 months

    Thigh muscle mass by Magnetic Resonance Imaging (MRI) using Dixon method.

  7. Skeletal muscle cross sectional area (CSA) of fibers

    Time frame: From randomization (month 0) to 12 months

    CSA of fibers by cryosection of skeletal muscle biopsy obtained from vastus lateralis muscle.

  8. Skeletal muscle tissue fiber composition

    Time frame: From randomization (month 0) to 12 months

    Change in ratio between muscle fiber types (type I, IIa and IIb) assessed by immunohistochemistry.

  9. Skeletal muscle tissue cellular composition

    Time frame: From randomization (month 0) to 12 months

    Change in muscle tissue cellular composition assessed by cell sorting

  10. Skeletal muscle mitochondrial function

    Time frame: From randomization (month 0) to 12 months

    Change in muscle mitochondrial function assessed by high-resolution respirometry

  11. Total lean body mass

    Time frame: From randomization (month 0) to 12 months

    Change in lean body mass (in grams) and total lean mass/height^2.

  12. Total body fat percentage

    Time frame: From randomization (month 0) to 12 months

    Changes in body fat percentage.

  13. Estimated visceral adipose tissue

    Time frame: From randomization (month 0) to 12 months

    Change in VAT index (kilogram-per-meters-squared index) and in mass (in grams).

  14. Intramuscular and intermuscular fat content

    Time frame: From randomization (month 0) to 12 months

    Calculating thigh adipose tissue mass located between and within muscle fibers by MRI Dixon method.

  15. Free fatty acids

    Time frame: From randomization (month 0) to 12 months

    Measured from blood samples.

  16. Insulin resistance

    Time frame: From randomization (month 0) to 12 months

    Changes in insulin resistance assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).

  17. Markers of autophagy

    Time frame: From randomization (month 0) to 12 months

    Proteomics of skeletal muscle tissue and peripheral blood mononuclear cells (PBMCs).

  18. Polyamine content in muscle biopsy

    Time frame: From randomization (month 0) to 12 months

    Measured with liquid chromatography mass spectrometry (LC-MS).

  19. Polyamine content in blood

    Time frame: From randomization (month 0) to 12 months

    Plasma samples obtained from blood. Measured with liquid chromatography mass spectrometry (LC-MS).

  20. Change in 24-hour ambulatory blood pressure measurements (24h ABPM)

    Time frame: From randomization (month 0) to 12 months

    Measured with the Spacelabs Healthcare 90217A device in an out-of-hospital setting.

  21. Change in central blood pressure

    Time frame: From randomization (month 0) to 12 months

    Measured noninvasive with pulse wave analysis (PWA) using a SphygmoCor system.

  22. Change in daily physical activity

    Time frame: From randomization (month 0) to 12 months

    Assessed by 14-day activity monitoring with an accelerometer (AX3, Axivity).

  23. Change in cardiac extracellular volume fraction

    Time frame: From randomization (month 0) to 12 months

    Assessed using Cardiac Magnetic Resonance Imaging (CMR) with intravenous gadolinium-based agent.

  24. Change in myocardial strain

    Time frame: From randomization (month 0) to 12 months

    Assessed using Cardiac Magnetic Resonance Imaging (CMR) with intravenous gadolinium-based agent.

  25. Change in Carotid-femoral pulse wave velocity

    Time frame: From randomization (month 0) to 12 months

    Measured non-invasively through applanation tonometry using a SphygmoCor system. The unit of measure is m/s.

  26. Change in Aortic pulse wave velocity

    Time frame: From randomization (month 0) to 12 months

    Magnetic resonance imaging (MRI) assessment. The unit of measure is m/s.

  27. Change in general cognitive function and memory performance

    Time frame: From randomization (month 0) to 12 months

    Evaluated using the Montreal Cognitive Assessment (MoCA). It will be administered in a clinical setting using a tablet. MoCA score ranges from 0-30 and a score of 26 or higher is considered normal.

  28. Change in specific domains of cognitive function

    Time frame: From randomization (month 0) to 12 months

    Evaluated using Cambridge Cognition (CANTAB) digital assessment software in a clinical setting using a tablet. The cognitive tests are MOT, RTI, SWM, DMS and PAL. These tests will objectively measure psychomotor speed, executive function and memory.

  29. HeartQol

    Time frame: From randomization (month 0) to 12 months

    HeartQol measures health-related quality of life (HRQL) and is a disease-specific health status instrument for ischemic heart disease. It consists of 14 items and provides two subscales; a 10-item physical subscale and a 4-item emotional subscale, which are scored on a four-point Likert scale (0 to 3). Higher scores indicate a better HRQL. Measured as global, physical and emotional score.

  30. Cytokines

    Time frame: From randomization (month 0) to 12 months

    Changes in cytokines are evaluated through the utilization of multiplex cytokine assays. Measured from plasma blood samples.

  31. White blood cells

    Time frame: From randomization (month 0) to 12 months

    Changes in white blood cell differential count.

  32. Immune cells

    Time frame: From randomization (month 0) to 12 months

    Changes in specific immune cell populations are measured using peripheral blood mononuclear cells (PBMCs) isolated from blood samples.

  33. Vascular inflammatory markers

    Time frame: From randomization (month 0) to 12 months

    Measured from plasma blood samples with a multiplex assay.

  34. Time to first occurrence of Composite cardiovascular endpoint: Cardiovascular death, heart failure hospitalizations, non-fatal myocardial infarction, non-fatal stroke, and coronary revascularization

    Time frame: From randomization (month 0) to 12 months

    Measured in months.

  35. Days alive and out of hospital

    Time frame: From randomization (month 0) to 12 months

    Measured in months.

Other outcomes

  1. Changes in gut microbiota

    Time frame: From randomization (month 0) to 12 months

    16S RNA analysis will be used for characterization of the bacterial composition.

    Full sequencing will be used for characterisation of the collective composition of bacteria, viruses, bacteriophages, fungi, and parasites.

  2. Changes in fecal metabolites

    Time frame: From randomization (month 0) to 12 months

    Mass spectrometric metabolome analyses will be used for assessing fecal metabolites before and after intervention.

  3. Skeletal muscle quality assesment

    Time frame: From randomization (month 0) to 12 months

    An explorative analysis of skeletal muscle quality including MRI with Dixon method, fiber CSA and type composition, tissue vascularity, morphology and architecture of skeletal muscle biopsy taken from vastus lateralis.

  4. Explorative analysis of adipose tissue

    Time frame: From randomization (month 0) to 12 months

    Measurement of enzymes involved in lipid storage. FACS to examine the cellular composition of the adipose tissue sample and to allow downstream PCR analysis of DNA/RNA or western blot analysis of proteins from specific cell populations or from non-sorted biopsy material.

  5. Explorative analysis of skeletal muscle tissue

    Time frame: From randomization (month 0) to 12 months

    FACS to examine the cellular composition and to allow downstream PCR analysis of DNA/RNA or western blot analysis of proteins from specific cell populations or from non-sorted biopsy material. RNA sequencing, and protein content will be assessed as metabolomics and proteomics by mass-spectrometry.

  6. Whole body metabolism

    Time frame: From randomization (month 0) to 12 months

    Changes in circulating metabolic markers

  7. Muscle metabolism

    Time frame: From randomization (month 0) to 12 months

    Changes in metabolic signature of muscle tissue assessed by liquid chromatography-high-resolution mass spectrometry

  8. Skeletal muscle satellite cell (MuSC) proliferation assays

    Time frame: From randomization (month 0) to 12 months

    Proliferation and differentiation analysis in cell numbers and cell viability of MuSC

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Collaborators

  • Aarhus University Hospital
  • Danish Cardiovascular Academy (DCA)
  • Danish Diabetes Academy
  • DoNotAge.org
  • Eva and Henry Frænkels Mindefond
  • Sygesikringen Danmark

Registry information

Official study title

Polyamine Treatment in Elderly Patients With Coronary Artery Disease - a Randomized Controlled Trial

Acronym: PolyCAD

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Dec 29, 2023
Registry last updated
Jul 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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