Clinical trial NCT06186102: Polyamine Treatment in Elderly Patients With Coronary Artery Disease
Official title: Polyamine Treatment in Elderly Patients With Coronary Artery Disease - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ischemic Heart Disease
Myocardial Infarction
Cardiovascular Diseases
Hypertensive Heart Disease
Hypertension
Diastolic Dysfunction
Obesity
Metabolic Syndrome
Diabetes Mellitus, Type 2
Dietary Habits
Inflammation
Quality of Life
Cognition Disorder
Cognitive Impairment
Keywords: Spermidine
Dietary supplement
Polyamine
Prevention
Treatment
Lifestyle
Coronary artery disease
Ischemic heart disease
Cardiovascular disease
Heart disease
Hypertension
Obesity
Diabetes Mellitus, Type 2
Insulin resistance
Inflammation
Quality of life
Cognitive function
Memory
Autophagy
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Sygesikringen Danmark
name: Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital
name: Danish Diabetes Academy
name: Danish Cardiovascular Academy (DCA)
name: Eva and Henry Frænkels Mindefond
name: DoNotAge.org
First posted: 2023-12-29
Enrollment: 180
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled, two-armed, parallel-group, single centre, clinical study.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in left ventricular mass
timeFrame: From randomization (month 0) to 12 months
measure: Change in appendicular lean mass and ALM index
timeFrame: From randomization (month 0) to 12 months
measure: Change in High-sensitivity C-reactive Protein (hs-CRP)
timeFrame: From randomization (month 0) to 12 months
measure: Change in Physical performance, peak oxygen consumption (VO2max)
timeFrame: From randomization (month 0) to 12 months
Secondary outcomes:
measure: Muscle strength, Handgrip strength
timeFrame: From randomization (month 0) to 12 months
measure: Muscle strength, Knee-extension/flexion strength
timeFrame: From randomization (month 0) to 12 months
measure: Physical performance, 6 minute walk test (6MWT)
timeFrame: From randomization (month 0) to 12 months
measure: Physical performance, 30 seconds sit to stand test
timeFrame: From randomization (month 0) to 12 months
measure: The Short Physical Performance Battery
timeFrame: From randomization (month 0) to 12 months
measure: Skeletal muscle mass
timeFrame: From randomization (month 0) to 12 months
measure: Skeletal muscle cross sectional area (CSA) of fibers
timeFrame: From randomization (month 0) to 12 months
measure: Skeletal muscle tissue fiber composition
timeFrame: From randomization (month 0) to 12 months
measure: Skeletal muscle tissue cellular composition
timeFrame: From randomization (month 0) to 12 months
measure: Skeletal muscle mitochondrial function
timeFrame: From randomization (month 0) to 12 months
measure: Total lean body mass
timeFrame: From randomization (month 0) to 12 months
measure: Total body fat percentage
timeFrame: From randomization (month 0) to 12 months
measure: Estimated visceral adipose tissue
timeFrame: From randomization (month 0) to 12 months
measure: Intramuscular and intermuscular fat content
timeFrame: From randomization (month 0) to 12 months
measure: Free fatty acids
timeFrame: From randomization (month 0) to 12 months
measure: Insulin resistance
timeFrame: From randomization (month 0) to 12 months
measure: Markers of autophagy
timeFrame: From randomization (month 0) to 12 months
measure: Polyamine content in muscle biopsy
timeFrame: From randomization (month 0) to 12 months
measure: Polyamine content in blood
timeFrame: From randomization (month 0) to 12 months
measure: Change in 24-hour ambulatory blood pressure measurements (24h ABPM)
timeFrame: From randomization (month 0) to 12 months
measure: Change in central blood pressure
timeFrame: From randomization (month 0) to 12 months
measure: Change in daily physical activity
timeFrame: From randomization (month 0) to 12 months
measure: Change in cardiac extracellular volume fraction
timeFrame: From randomization (month 0) to 12 months
measure: Change in myocardial strain
timeFrame: From randomization (month 0) to 12 months
measure: Change in Carotid-femoral pulse wave velocity
timeFrame: From randomization (month 0) to 12 months
measure: Change in Aortic pulse wave velocity
timeFrame: From randomization (month 0) to 12 months
measure: Change in general cognitive function and memory performance
timeFrame: From randomization (month 0) to 12 months
measure: Change in specific domains of cognitive function
timeFrame: From randomization (month 0) to 12 months
measure: HeartQol
timeFrame: From randomization (month 0) to 12 months
measure: Cytokines
timeFrame: From randomization (month 0) to 12 months
measure: White blood cells
timeFrame: From randomization (month 0) to 12 months
measure: Immune cells
timeFrame: From randomization (month 0) to 12 months
measure: Vascular inflammatory markers
timeFrame: From randomization (month 0) to 12 months
measure: Time to first occurrence of Composite cardiovascular endpoint: Cardiovascular death, heart failure hospitalizations, non-fatal myocardial infarction, non-fatal stroke, and coronary revascularization
timeFrame: From randomization (month 0) to 12 months
measure: Days alive and out of hospital
timeFrame: From randomization (month 0) to 12 months
Other outcomes:
measure: Changes in gut microbiota
timeFrame: From randomization (month 0) to 12 months
measure: Changes in fecal metabolites
timeFrame: From randomization (month 0) to 12 months
measure: Skeletal muscle quality assesment
timeFrame: From randomization (month 0) to 12 months
measure: Explorative analysis of adipose tissue
timeFrame: From randomization (month 0) to 12 months
measure: Explorative analysis of skeletal muscle tissue
timeFrame: From randomization (month 0) to 12 months
measure: Whole body metabolism
timeFrame: From randomization (month 0) to 12 months
measure: Muscle metabolism
timeFrame: From randomization (month 0) to 12 months
measure: Skeletal muscle satellite cell (MuSC) proliferation assays
timeFrame: From randomization (month 0) to 12 months
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
state: Jutland
Study officials:
affiliation: Dept. of Cardiology, Aarhus University Hospital
name: Henrik Wiggers, DMSC PHD MD
role: PRINCIPAL_INVESTIGATOR
References: