PHOspholamban RElated CArdiomyopathy STudy - Intervention

• Status: Completed
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Phospholamban (PLN) R14del mutation carriers may develop dilated cardiomyopathy (DCM) and/or arrhythmmogenic cardiomyopathy (ACM). Analogous to other inherited cardiomyopathies, the natural course of the disease is age-related ("age-related penetrance"); after a presymptomatic phase of variable length many PLN R14del-carriers progress to overt disease, and are diagnosed with either DCM or ARVC. PLN is a regulator of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) pump in cardiac muscle and thereby important for maintaining Ca2+ homeostasis. Cardiac fibrosis appears to be an early manifestation of disease. The investigators hypothesize that treatment of presymptomatic PLN R14del-carriers with eplerenone, which by virtue of its mineralocorticoid(aldosterone)-blocking properties is a strong antifibrotic agent, reduces disease progression and postpones onset of overt disease.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.p. van den Berg, MD, PhD, professor in Cardiology
• Collaborators: Netherlands: CVON, CardioVascular Research Netherlands; Netherlands: TCC, Trial Coordination Center UMCG; The Interuniversity Cardiology Institute of the Netherlands; University Medical Center Groningen; ZonMw: The Netherlands Organisation for Health Research and Development
• Treatments: Eplerenone; Spironolactone

Criteria

Inclusion Criteria:

• Phospholamban (PLN) R14del mutation carriers

• Age ≥30 and ≤ 65 years

• New York Heart Association functional class ≤ 1

• LV ejection fraction ≥.45 (measured with MRI)

Exclusion Criteria:

• Palpitations necessitating treatment (at the discretion of the attending physician)

• A diagnosis of DCM (see appendix 1). Note: regional LV wall motions abnormalities are acceptable.

• A diagnosis of ARVC (according to the task force criteria, see appendix 2)

• Global or regional RV dysfunction and/or structural alterations (according to task force criterion 1, see appendix 2).

• Ventricular premature complexes >1000 during 24hours Holter-monitoring

• Non-sustained ventricular tachycardia during Holter-monitoring or exercise-testing

• History of sustained ventricular tachycardia or ventricular fibrillation

• Hypertension requiring the use of antihypertensive drugs, or when this is anticipated within the coming 3 years

• Evidence of ischemic heart disease

• Treatment with cardioactive medication

• Hyperkaliemia (serum potassium >5.0 mmol/l)

• Severe renal dysfunction (eGFR <30 ml/min/1.73 m2)

• Severe hepatic impairment (Child-Pugh class C)

• Women who are currently pregnant or report a recent pregnancy (last 60 days) or plan on becoming pregnant.

• Concomitant use of CYP3A4-inhibitors (see appendix 5)

• Concomitant use of NSAIDs (see appendix 5)

• Concomitant use of potassium sparing-agents (see appendix 5)

• Known intolerance or contraindication to aldosterone antagonists

• Participation in another drug trial in which the last dose of drug was within the past 30 days.

• Contra-indications for MRI (claustrophobia, metal devices)

• Subjects unable or unwilling to provide written informed consent