A Clinical Trial, Investigating the Effect of a Home-based Moderate Intensity Training Program on Oxidative Capacity and Hemodynamics in Patients With Truncating Genetic Variants in TTN.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Difference in change in peak oxygen uptake (VO2peak) as measured in an incremental cycle-ergometer exercise test to exhaustion, in the placebo vs intervention period
研究概览
简要总结
The aim is to investigate the effect of an 8-week moderate-intensity exercise program on aerobic fitness and cardiac contractility in patients with truncations of the sarcomeric protein titin.
详细描述
Mutations leading to truncations of the large sarcomeric protein titin was discovered in 2012 as the most prevalent genetic cause of familial dilated cardiomyopathy, affecting approximately 25% of all cases of familial dilated cardiomyopathy. The dilated cardiomyopathy phenotype associated with truncating titin variants (TTNtv) is associated with a high prevalence of arrhythmias but is generally thought to represent a relatively mild DCM phenotype, which often responds well to medical therapy.
In vitro experiments on human induced pluripotent stem cells show that TTNtv leads to sarcomere insufficiency, impaired responses to mechanical and β-adrenergic stress, and attenuated growth factor and cell signaling activation. Experiments in animal models suggest patients with TTNtv are intolerant to long-lasting hemodynamic stress. This finding is supported by clinical studies in which a significant proportion of patients with peripartum cardiomyopathy, alcoholic cardiomyopathy and chemotherapy-induced cardiomyopathy were found to carry TTNtv.
So far, no interventional studies have been carried out specifically in patients with TTNtv. In an older study putative variants in TTN have been suggested to be associated with cardiac adaptations to endurance training, namely the rate of change in stroke volume during submaximal exercise.
Previous interventional exercise-studies in patients with a range of mutations in genes encoding proteins of the cytoskeleton, sarcomere, ion-channels and enzymes of the mitochondrial respiratory chain, safely improves oxidative fitness. Studies carried out on patients with heart failure of mixed etiologies and in patients with hypertrophic cardiomyopathy reveals similar beneficial effects of exercise. These studies reject the idea that training "diseased" muscle tissue leads to further muscle damage or is ineffective.
Many patients with cardiomyopathy often lead a sedentary life but aspire to live a physically active lifestyle and take advantage of the many documented health benefits of exercise. However, recommendations for engaging in physical activity in patients with heart failure and cardiomyopathies are vague since proper evidence does not exist for each genetic disorder.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Mutations in the TTN gene leading to truncating variants in cardiac expressed exons of titin.
- •A clinical diagnosis of dilated cardiomyopathy or fulfulling criteria for the diagnosis of heart failure or hypokinetic non-dilated cardiomyopathy.
排除标准
- •New York Heart Association functional class IV.
- •Patients with a left ventricular assist device or who have had a heart transplant.
- •Change in heart failure medications within the last month.
- •CRT implantation within the last 6 months.
- •Inability to perform exercise due to orthopedic or other non-cardiovascular limitations.
- •Clinical history of exercise-induced syncope likely caused by ventricular tachyarrhythmias.
- •Current participation in moderate or high intensity exercise exceeding 2.5 hours/per week.
- •Inability to give informed consent.
- •Pregnant women.
- •Severe vascular disease (IE claudicatio intermittens).
- •Severe valvular disease (moderate aortic stenosis/regurgitation or severe mitral regurgitation/stenosis).
- •Life expectancy less than 12 months.
- •Expected reduced compliance.
结局指标
主要结局
Difference in change in peak oxygen uptake (VO2peak) as measured in an incremental cycle-ergometer exercise test to exhaustion, in the placebo vs intervention period
时间窗: 8 weeks
The VO2peak will be defined as the 20 consecutive seconds with the highest average VO2 during the incremental cycle-ergometer exercise test to exhaustion.
次要结局
- Changes in cardiac and skeletomuscular biomarkers (CKMB, CK, NT proBNP, myoglobin, TnT, TnI)(8 weeks)
- Difference in change in left ventricular stroke volume at approximately 50% of maximal exertion in the placebo vs intervention period.(8 weeks)
- Difference in change in cardiac output at 100% of VO2peak, in the placebo vs intervention period.(8 weeks)
- Difference in change in left ventricular stroke volume at 100% of VO2peak, in the placebo vs intervention period.(8 weeks)
- Left ventricular volumetric measures from 3D echocardiography(8 weeks)
- Change in systemic blood pressure(8 weeks)
- Quality of life indicators as measured in the Short Form Health Survey (SF-36)(8 weeks)
- Change in hemoglobin mass with training.(8 weeks)
- Difference in change in cardiac output at approximately 50% of maximal exertion in the placebo vs intervention period.(8 weeks)
- Global longitudinal strain as measured by echocardiography(8 weeks)
- Maximal workload in the maximal exercise test(8 weeks)
- Change in blood volume with training.(8 weeks)
- Difference in change in cardiac index at rest and during exercise(8 weeks)
- Performance in a 6-minute walk test(8 weeks)
研究者
Ida Finsen Flensted
Bach.med.
Rigshospitalet, Denmark