Polyamine Treatment in Elderly Patients With Coronary Artery Disease - a Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 187
- 试验地点
- 2
- 主要终点
- Change in left ventricular mass
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double (Participant, Investigator)
入排标准
- 年龄范围
- 65 Years 至 90 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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)
研究组 & 干预措施
Placebo
Placebo will be given orally as capsules of cellulose and rice flour (same size and visual appearance as spermidine capsules)
干预措施: Placebo (Other)
Spermidine
Spermidine will be given orally as capsules of cellulose with spermidine (24 mg/day) and rice flour.
干预措施: Spermidine (Dietary Supplement)
结局指标
主要结局
Change in left ventricular mass
时间窗: From randomization (month 0) to 12 months
Measured with Cardiac Magnetic Resonance Imaging (CMR).
Change in appendicular lean mass and ALM index
时间窗: 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.
Change in Physical performance, peak oxygen consumption (VO2max)
时间窗: 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.
Change in High-sensitivity C-reactive Protein (hs-CRP)
时间窗: From randomization (month 0) to 12 months
Measured from blood samples.
次要结局
- Muscle strength, Handgrip strength(From randomization (month 0) to 12 months)
- Skeletal muscle mass(From randomization (month 0) to 12 months)
- Skeletal muscle tissue cellular composition(From randomization (month 0) to 12 months)
- Physical performance, 30 seconds sit to stand test(From randomization (month 0) to 12 months)
- Estimated visceral adipose tissue(From randomization (month 0) to 12 months)
- Insulin resistance(From randomization (month 0) to 12 months)
- Polyamine content in muscle biopsy(From randomization (month 0) to 12 months)
- Change in central blood pressure(From randomization (month 0) to 12 months)
- Change in myocardial strain(From randomization (month 0) to 12 months)
- HeartQol(From randomization (month 0) to 12 months)
- White blood cells(From randomization (month 0) to 12 months)
- Days alive and out of hospital(From randomization (month 0) to 12 months)
- Change in 24-hour ambulatory blood pressure measurements (24h ABPM)(From randomization (month 0) to 12 months)
- The Short Physical Performance Battery(From randomization (month 0) to 12 months)
- Skeletal muscle cross sectional area (CSA) of fibers(From randomization (month 0) to 12 months)
- Skeletal muscle mitochondrial function(From randomization (month 0) to 12 months)
- Markers of autophagy(From randomization (month 0) to 12 months)
- Muscle strength, Knee-extension/flexion strength(From randomization (month 0) to 12 months)
- Physical performance, 6 minute walk test (6MWT)(From randomization (month 0) to 12 months)
- Intramuscular and intermuscular fat content(From randomization (month 0) to 12 months)
- Free fatty acids(From randomization (month 0) to 12 months)
- Change in Aortic pulse wave velocity(From randomization (month 0) to 12 months)
- Change in general cognitive function and memory performance(From randomization (month 0) to 12 months)
- Cytokines(From randomization (month 0) to 12 months)
- Immune cells(From randomization (month 0) to 12 months)
- Skeletal muscle tissue fiber composition(From randomization (month 0) to 12 months)
- Total lean body mass(From randomization (month 0) to 12 months)
- Total body fat percentage(From randomization (month 0) to 12 months)
- Change in specific domains of cognitive function(From randomization (month 0) to 12 months)
- Vascular inflammatory markers(From randomization (month 0) to 12 months)
- Polyamine content in blood(From randomization (month 0) to 12 months)
- Change in daily physical activity(From randomization (month 0) to 12 months)
- Change in Carotid-femoral pulse wave velocity(From randomization (month 0) to 12 months)
- Change in cardiac extracellular volume fraction(From randomization (month 0) to 12 months)
- Time to first occurrence of Composite cardiovascular endpoint: Cardiovascular death, heart failure hospitalizations, non-fatal myocardial infarction, non-fatal stroke, and coronary revascularization(From randomization (month 0) to 12 months)