Polyamine Treatment in Elderly Patients With Coronary Artery Disease (PolyCAD)

University of Aarhus

Status and phase: Enrolling; Phase 2

Conditions: Inflammation; Dietary Habits; Diastolic Dysfunction; Cognitive Impairment; Obesity; Cardiovascular Diseases; Myocardial Infarction; Diabetes Mellitus, Type 2; Metabolic Syndrome; Hypertensive Heart Disease; Hypertension; Ischemic Heart Disease; Quality of Life; Cognition Disorder

Treatments: Dietary Supplement: Spermidine; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06186102

M-2023-71-23

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 180 estimated patients

Sex: All

Ages: 65 to 90 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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180 participants in 2 patient groups, including a placebo group

Spermidine

Active Comparator group

Description:

Spermidine will be given orally as capsules of cellulose with spermidine (24 mg/day) and rice flour.

Treatment:

Dietary Supplement: Spermidine

Placebo

Placebo Comparator group

Description:

Placebo will be given orally as capsules of cellulose and rice flour (same size and visual appearance as spermidine capsules)

Treatment:

Other: Placebo