Oxford - Fibrates in Aortic Stenosis

• Status: Active, not recruiting
• Trial end date: 2022-03-31
• Target enrollment: 0
• Participant gender: All

Summary

Aortic stenosis (AS) is characterised by left ventricular (LV) hypertrophy and altered myocardial substrate metabolism. Peroxisome proliferator-activated receptor (PPARα), a regulator of lipid metabolism is deactivated in pressure overload hypertrophy such as in AS and can lead to dysregulation of fatty acid oxidation, myocardial triglyceride accumulation (steatosis) and lipotoxicity. The investigators propose a proof-of-concept study to investigate the effect of altering myocardial triglyceride (MTG) using a PPARα agonist, fenofibrate on cardiac physiology in patients with asymptomatic moderate-severe AS. The primary endpoint is a change in MTG assessed by magnetic resonance spectroscopy at baseline and after 6 months of treatment. Exploratory endpoints are changes in cardiac physiology including myocardial deformation (strain) as assessed by cardiac magnetic resonance imaging. The investigators hypothesise that pharmacological reduction of MTG with a PPARα agonist will result in steatosis regression and changes in cardiac physiology.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Oxford
• Collaborator: British Heart Foundation
• Treatments: Fenofibrate

Criteria

Inclusion Criteria:

• Asymptomatic moderate to severe AS (with at least two of the following: aortic valve area <1.5 cm2, peak pressure gradient >36 mmHg or mean pressure gradient >25 mmHg)

• Not planned aortic valve replacement or transcatheter aortic valve implantation (TAVI)

• Age >18

• No other significant valvular pathology

• No contraindication to magnetic resonance imaging.

Exclusion Criteria:

• Known coronary artery disease, history of angina, myocardial infarction or presence of regional wall motion abnormalities

• Other underlying cardiomyopathy

• Left ventricular ejection fraction<50%

• Uncontrolled hypertension

• Diabetes Mellitus

• Liver impairment

• Pregnancy and lactation

• Body mass index >35 kg/m2

• Renal impairment (eGFR<30 ml/min)

• Intolerance to or concurrent use of fibrates or PPARα agonists.