Cardiac Rehabilitation in Patients With High-Genetic-Risk Arrhythmogenic Cardiomyopathy: The HGEN-CARE-AC Trial (HGEN-CARE-AC)
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)
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.
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Descrizione dettagliata
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:
Safety and structural remodeling will be monitored throughout the study period. Safety assessments include continuous surveillance for adverse events (e.g., symptomatic arrhythmias, syncope, or hospitalizations). Structural and functional cardiac changes will be quantified through standardized advanced cardiac imaging techniques (echocardiography) and cardiopulmonary exercise testing at baseline and follow-up time points. Psychometric status will be evaluated using validated questionnaires to capture changes in health-related quality of life, anxiety, and depression.
Statistical Analysis Plan:
Continuous variables will be reported as mean ± standard deviation (or median and interquartile range for non-normal distributions), while categorical variables will be presented as frequencies and percentages. Longitudinal changes from baseline to follow-up will be evaluated using mixed-effects models for repeated measures, accounting for inter-individual variability.
An exploratory subgroup analysis will be conducted to assess the consistency of the intervention's effects across predefined patient strata. Differences in safety and efficacy outcomes (such as changes in VO2 peak and left ventricular ejection fraction) will be evaluated, stratified by:
- Biological Sex: Categorized as male or female.
- Causal Genotype: Categorized by the identified pathogenic variant (LMNA, DSP, FLNC, TMEM43, PLN, or DES).
Statistical comparisons between subgroups will be performed using independent t-tests or ANOVA for normally distributed continuous data, and Mann-Whitney U or Kruskal-Wallis tests for non-normally distributed data. Categorical variables will be assessed using Chi-square or Fisher's exact tests. This exploratory analysis is intended to identify potential heterogeneous treatment effects; all tests will be two-tailed, with a p-value < 0.05 considered statistically significant.
Tipo di studio
Tipo di studio
Iscrizione (Stimato)
Iscrizione
Fase
Fase
- Non applicabile
Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
- Adulto
- Adulto più anziano
Accetta volontari sani
Descrizione
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
|---|---|
|
Sperimentale: 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).
|
A structured, personalized, and supervised cardiac rehabilitation program based on moderate-intensity physical exercise, tailored specifically for high-risk genotype-positive arrhythmogenic cardiomyopathy (ACM) patients. The intervention follows the FITT (Frequency, Intensity, Time, Type) principles: Frequency: 2 to 3 supervised sessions per week for a total duration of 12 consecutive weeks. Intensity: Strictly restricted to a moderate-intensity zone. The target training heart rate is set individually, bounded between the first ventilatory threshold (VT1) and a safe ceiling well below the second ventilatory threshold (VT2) or any individual arrhythmic thresholds identified during baseline cardiopulmonary exercise testing (CPET). Time: Each session lasts between 90 minutes, including a 10-minute progressive warm-up and a 10-minute cool-down phase. Type: Continuous aerobic exercise primarily performed on a cycle ergometer o |
|
Nessun intervento: 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.
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Composite safety endpoint of clinical and arrhythmic events.
Lasso di tempo: 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.
|
From baseline up to 6 months.
|
Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Change from baseline in peak oxygen consumption (VO2 peak)
Lasso di tempo: Baseline and 12 weeks
|
Change in peak oxygen consumption (VO2 peak).
Breath-by-breath gas exchange measurements (oxygen uptake in mL/min and carbon dioxide production in mL/min) and total body weight in kilograms (Kg) will be combined to report VO2 peak in mL/kg/min.
This value represents the highest 30-second average of oxygen consumption attained during the maximal effort stage of a cardiopulmonary exercise test (CPET).
|
Baseline and 12 weeks
|
|
Change from baseline in metabolic equivalents (METs)
Lasso di tempo: Baseline and 12 weeks
|
Preliminary clinical efficacy on functional capacity will be evaluated using objective cardiopulmonary metrics.
Change in metabolic equivalents (METs).
Peak oxygen uptake (mL/kg/min) and the resting metabolic constant (3.5 mL/kg/min) will be combined to report the peak METs achieved during maximal cardiopulmonary exercise testing (CPET).
This value is calculated as the ratio of peak oxygen consumption to the resting metabolic rate.
|
Baseline and 12 weeks
|
|
Change from baseline in 6-minute walk distance
Lasso di tempo: Baseline and 12 weeks.
|
Change in total distance walked during the 6-Minute Walk Test (6MWT).
Walking speed (m/s) and the duration of the test (6 minutes) will be combined to report the total distance covered in meters.
The distance is measured from start to finish based on the participant's total displacement during the 6-minute period.
|
Baseline and 12 weeks.
|
|
Change in left ventricular ejection fraction (LVEF)
Lasso di tempo: Baseline and 6 months.
|
Exploratory changes in the phenotypic expression of arrhythmogenic cardiomyopathy will be evaluated with echocardiogram to monitor mid-term structural remodeling. Left ventricular end-diastolic volume (mL) and end-systolic volume (mL) will be combined to report the LVEF as a percentage (%). This value is calculated as the stroke volume divided by the end-diastolic volume. Unit of Measure: Percentage (%) |
Baseline and 6 months.
|
|
Change in right ventricular ejection fraction (RVEF)
Lasso di tempo: Time Frame: Baseline and 6 months.
|
Exploratory changes in the phenotypic expression of arrhythmogenic cardiomyopathy will be evaluated with echocardiogram to monitor mid-term structural remodeling. Right ventricular end-diastolic volume (mL) and end-systolic volume (mL) will be combined to report the RVEF as a percentage (%). This value is calculated as the stroke volume divided by the end-diastolic volume. Unit of Measure: Percentage (%) |
Time Frame: Baseline and 6 months.
|
|
Change in left ventricular internal diameter
Lasso di tempo: Baseline and 6 months.
|
Exploratory changes in the phenotypic expression of arrhythmogenic cardiomyopathy will be evaluated with echocardiogram to monitor mid-term structural remodeling. Endocardial-to-endocardial distances in the parasternal long-axis view will be combined to report the diameter at end-diastole. Unit of Measure: Millimeters (mm) |
Baseline and 6 months.
|
|
Change from baseline in Body Mass Index (BMI)
Lasso di tempo: Baseline and 12 weeks.
|
Impact on general cardiovascular health parameters will be analyzed through BMI: Total body weight (Kg) and height (m) will be combined to report BMI in kg/m2. Unit of Measure: kg/m2 |
Baseline and 12 weeks.
|
|
Change from baseline in systolic blood pressure
Lasso di tempo: Baseline and 12 weeks.
|
Impact on general cardiovascular health parameters will be analyzed through multiple blood pressure readings taken at rest will be combined (averaged) to report the systolic blood pressure. Unit of Measure: mmHg |
Baseline and 12 weeks.
|
|
Change from baseline in serum LDL cholesterol
Lasso di tempo: Baseline and 12 weeks.
|
Impact on general cardiovascular health parameters will be analyzed through LDL levels. Total cholesterol, HDL cholesterol, and triglyceride measurements will be combined using the Friedewald equation to report the calculated LDL cholesterol concentration. Unit of Measure: mg/dL |
Baseline and 12 weeks.
|
|
Change from baseline in glycated hemoglobin (HbA1c)
Lasso di tempo: Baseline and 12 weeks.
|
Glycated hemoglobin levels will be measured from venous blood samples to report the percentage of hemoglobin A1c. Unit of Measure: Percentage (%) |
Baseline and 12 weeks.
|
|
Change from baseline in Hospital Anxiety and Depression Scale (HADS) score
Lasso di tempo: Baseline and 6 months.
|
The psychological impact of the rehabilitation program will be assessed using validated psychometric scales. Change in anxiety and depression levels. Individual item scores (responses to 14 questions) will be combined to report the total HADS score. This scale aggregates responses to assess anxiety and depression symptoms; higher scores indicate greater symptom severity (a worse outcome). Unit of Measure: Scale (on a scale of 0 to 42) |
Baseline and 6 months.
|
|
Change from baseline in SF-36 health-related quality of life score
Lasso di tempo: Baseline and 6 months.
|
The psychological impact of the rehabilitation program will be assessed using validated psychometric scales. Change in health-related quality of life. The 36 individual item responses will be combined and weighted using standard scoring algorithms to report the SF-36 summary scores (Physical and Mental Component Summary scores); higher scores indicate a better health-related quality of life (a better outcome). Unit of Measure: Scale (on a scale of 0 to 100) |
Baseline and 6 months.
|
|
Change from baseline in EQ-5D-5L index score
Lasso di tempo: Baseline and 6 months.
|
The psychological impact of the rehabilitation program will be assessed using validated psychometric scales. Change in health-related quality of life. Responses to the 5 dimensions are combined using an official value set to report a single index score; higher scores indicate a better health state (a better outcome). Unit of Measure: Scale (0 to 1) |
Baseline and 6 months.
|
Collaboratori e investigatori
Sponsor
Sponsor
Collaboratori
Collaboratori
Studiare le date dei record
Studia le date principali
Inizio studio (Stimato)
Inizio studio
Completamento primario (Stimato)
Completamento primario
Completamento dello studio (Stimato)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- HGEN-CARE-AC STUDY
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .