Exploratory Randomized Clinical Trial on the Safety and Feasibility of a Cardiac Rehabilitation Programme in Patients With High-Genetic-Risk Arrhythmogenic Cardiomyopathy (HGEN-CARE-AC Study)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 70
- 主要终点
- Composite safety endpoint of clinical and arrhythmic events.
研究概览
简要总结
The goal of this clinical trial is to evaluate a structured and personalized cardiac rehabilitation program for patients diagnosed with arrhythmogenic cardiomyopathy (ACM) who carry high-risk genetic mutations. Historically, physical exercise has been strictly restricted in these patients due to the potential risk of triggering life-threatening arrhythmias and accelerating structural heart disease. However, complete inactivity leads to severe physical deconditioning and reduced quality of life. This study aims to address this clinical dilemma by investigating a safe way to prescribe exercise.
The primary research question is: Is a supervised, moderate-intensity exercise program safe, and does it avoid increasing the risk of cardiac arrhythmias or worsening right ventricular function compared to standard physical restriction?
Secondary objectives include the evaluation of the impact of this tailored physical intervention on the participants' functional capacity, specifically measuring changes in physical fitness and peak oxygen consumption through cardiovascular testing. Additionally, the trial assesses the psychological benefits of the program, analyzing its effects on health-related quality of life, anxiety, and depression levels. The experimental group undergoing cardiac rehabilitation will be compared to a control group receiving conventional physical restriction guidelines to determine if the program is both safe and comprehensive.
详细描述
Study Design:
This is an exploratory, randomized, parallel-group clinical trial designed to assess the safety and feasibility of a structured cardiac rehabilitation program for patients with high-genetic-risk arrhythmogenic cardiomyopathy (ACM). Participants will be randomized in a 1:1 ratio to either the experimental intervention group or a control group receiving standard-of-care physical restriction guidelines.
Interventions:
- Experimental Group: Participants will undergo a 12-week supervised cardiac rehabilitation program. This intervention involves individualized, moderate-intensity exercise sessions. The intensity of the exercise prescription will be titrated based on baseline cardiopulmonary exercise testing (CPET) and individual cardiovascular risk profiles, aiming to improve functional capacity while minimizing the risk of pro-arrhythmic events.
- Control Group: Participants will follow conventional standard-of-care recommendations, which emphasize physical activity restriction as per current clinical practice guidelines for high-risk ACM.
Data Acquisition and Monitoring:
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
- 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
- •Participant must be 18 years of age or older at the time of signing the informed consent.
- •Definite diagnosis of arrhythmogenic cardiomyopathy (ACM) according to the 2024 European Task Force criteria.
- •Documented left or right ventricular involvement confirmed via transthoracic echocardiography or cardiac magnetic resonance imaging (MRI), characterized by abnormalities in regional contractility, presence of aneurysms, reduced ejection fraction, and/or late gadolinium enhancement (LGE).
- •Confirmed presence of a pathogenic or likely pathogenic genetic variant in the LMNA, DSP, FLNC, TMEM43, PLN, or DES genes.
- •Clinical stability maintained for 3 months or longer prior to inclusion, defined as the absence of hospital admissions, sustained ventricular arrhythmic events, or implantable cardioverter-defibrillator (ICD) shocks.
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
排除标准
- •Inability or physical contraindication to perform physical exercise at the time of inclusion.
- •Presence of overlapping phenotypes associated with other non-arrhythmogenic cardiomyopathies.
- •Active pregnancy.
- •Current engagement in competitive or high-intensity sports or exercise programs at the time of inclusion.
研究组 & 干预措施
Cardiac Rehabilitation Program
Participants randomized to this experimental arm will engage in a structured, personalized, and supervised physical exercise program at the hospital's specialized Cardiac Rehabilitation Unit for a duration of 12 weeks. The intervention consists of customized, moderate-intensity training sessions designed and supervised by qualified clinical personnel. Training intensity is strictly individualized, bounded by safe target heart rate thresholds and workloads derived from each participant's baseline maximal cardiopulmonary exercise testing (CPET).
干预措施: Cardiac Rehabilitation Programme (Behavioral)
Standard Physical Restriction
Participants randomized to this active comparator control arm will maintain conventional clinical care as prescribed by current guidelines for high-genetic-risk arrhythmogenic cardiomyopathy. This involves strict adherence to physical restriction guidelines, including complete abstinence from competitive, high-intensity sports and strenuous physical exercise. Participants are encouraged to maintain basic activities of daily living and light leisure-time physical habits, serving as a direct control baseline to evaluate safety outcomes.
结局指标
主要结局
Composite safety endpoint of clinical and arrhythmic events.
时间窗: From baseline up to 6 months.
Safety of the 12-week supervised moderate-intensity exercise program will be evaluated as a composite endpoint defined by the absence of a clinically relevant increase in ventricular arrhythmias or major adverse cardiovascular events. Arrhythmic safety includes ventricular arrhythmia burden (sustained and non-sustained ventricular tachycardia) detected via prolonged ambulatory Holter monitoring and ICD (Implantable Cardioverter-Defibrillator) interrogation logs. Clinical safety events track the incidence of major complications during the study period, including sudden cardiac death, appropriate or inappropriate ICD therapies (shocks or antitachycardia pacing), and arrhythmic syncope, comparing the intervention cohort against the standard physical restriction control group.
次要结局
- Change from baseline in peak oxygen consumption (VO2 peak)(Baseline and 12 weeks)
- Change from baseline in metabolic equivalents (METs)(Baseline and 12 weeks)
- Change from baseline in 6-minute walk distance(Baseline and 12 weeks.)
- Change in left ventricular ejection fraction (LVEF)(Baseline and 6 months.)
- Change in right ventricular ejection fraction (RVEF)(Time Frame: Baseline and 6 months.)
- Change in left ventricular internal diameter(Baseline and 6 months.)
- Change from baseline in Body Mass Index (BMI)(Baseline and 12 weeks.)
- Change from baseline in systolic blood pressure(Baseline and 12 weeks.)
- Change from baseline in serum LDL cholesterol(Baseline and 12 weeks.)
- Change from baseline in glycated hemoglobin (HbA1c)(Baseline and 12 weeks.)
- Change from baseline in Hospital Anxiety and Depression Scale (HADS) score(Baseline and 6 months.)
- Change from baseline in SF-36 health-related quality of life score(Baseline and 6 months.)
- Change from baseline in EQ-5D-5L index score(Baseline and 6 months.)
研究者
Juan Jiménez Jáimez
MD, PhD, Head of the Arrhythmia and Familial Cardiopathies Unit in Virgen de las Nieves Hospital in Granada, Spain
Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental