Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction (CARE-AMI)

Insel Gruppe AG, University Hospital Bern

Status and phase

Completed

Phase 2

Conditions

Cardiac Remodeling

Myocardial Infarction

Treatments

Drug: Paroxetine

Drug: Placebo oral capsule

Study type

Interventional

Funder types

Other

Identifiers

NCT03274752

2016-00349

Details and patient eligibility

About

This study evaluates the off-target effect of paroxetine to reverse cardiac remodeling and improve left ventricular ejection fraction in patients after acute myocardial infarction. Half of the participants will receive paroxetine, while the other half will receive placebo treatment.

Full description

Cardiac remodeling is characterized by a composite of structural, geometric, molecular, and functional changes of the myocardium, and is an important determinant of heart failure and cardiovascular outcome in survivors of acute myocardial infarction. Progression of heart failure secondary to the remodeling process results from dysregulation of the G protein-coupled receptor (GPCR). Excessive adrenergic drive in patients with heart failure results in an enhanced activation of GPCR kinases (GRKs) that is considered to have a central role in adverse cardiac remodeling after ischemic injury. The selective Serotonin reuptake inhibitor paroxetine specifically binds to the catalytic domain of GRK2 as an off-target effect, and has been shown to reverse cardiac remodeling and increase left ventricular ejection fraction in a mouse model. The effect was observed at serum levels achieved with standard dosages of paroxetine, and was robust in mice with and without concomitant heart failure treatment, respectively.

Enrollment

50 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Anterior wall ST-segment elevation myocardial infarction
Primary percutaneous coronary intervention (PCI) within 24 hours of symptom onset
Left ventricular ejection fraction ≤ 45% within 48-96 hours after primary PCI (transthoracic echocardiography)

Exclusion criteria

Female patients at reproductive age (<50 years)
Known intolerance to paroxetine
Inability to provide informed consent
Currently participating in another trial before reaching first endpoint
Current medical therapy with MAO-blocker (during, 14 days before, and 14 days after treatment with MAO-blocker), lithium, thioridazide, or pimozide
Concomitant tamoxifen intake
Previous myocardial infarction
Previous revascularization procedure (percutaneous coronary intervention or coronary artery bypass grafting).
Contraindication to cardiac magnetic resonance imaging
Obvious or questionable inability to appropriately cooperate (alcohol, drugs etc.)
Relevant nephropathy or hepatopathy