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A multi-center randomized, placebo-controlled trial of mirabegron, a new beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease

Objective

Patients with cardiovascular risk factors, e.g. hypertension and obesity are at risk of developing heart failure with preserved ejection fraction (HFpEF), a highly prevalent disease in the elderly, mostly women population. There is currently no specific, defined treatment for HFpEF, beyond control of risk factors. Activation of cardiac and vascular Beta3-adrenergic receptors (B3AR) represents a new concept and a novel target for structural cardiac disease. B3AR expression and coupling were demonstrated in human myocardium and vasculature. In pre-clinical models with expression of the human receptor, its activation attenuates myocardial remodelling, i.e. decreases hypertrophy and fibrosis in response to neurohormonal or hemodynamic stress. Mirabegron is a new agonist of B3AR available for human use, that was recently introduced for a non-cardiovascular indication (overactive bladder disease). The primary objective of the project is to design and implement a multi-centric, prospective, randomized, placebo-controlled clinical trial testing the additional beneficial effect of mirabegron, versus placebo over 12 months on top of standard treatment of patients carrying structural cardiac disease without overt heart failure (stage B of AHA classification); the co-primary end-point will be the quantitative change in myocardial hypertrophy measured by cardiac MRI; and in diastolic ventricular function, measured by Doppler echocardiography (E/E’); in addition, exercise tolerance (peak VO2) will be measured as well as circulating biomarkers reflecting both myocardial remodeling and function. In addition, we will test the effect of mirabegron on beige/brown fat activation and metabolism. Our proposal therefore combines a major conceptual advance and repurposing of an original drug to validate pre-clinical discoveries in the context of a major health problem.

Call for proposal

H2020-PHC-2014-two-stage
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

Coordinator

UNIVERSITE CATHOLIQUE DE LOUVAIN
Address
Place De L Universite 1
1348 Louvain La Neuve
Belgium
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 819 545,51

Participants (11)

UNIWERSYTET MEDYCZNY IM PIASTOW SLASKICH WE WROCLAWIU
Poland
EU contribution
€ 480 615
Address
Ul Pasteura 1
50 367 Wroclaw
Activity type
Higher or Secondary Education Establishments
Associação para Investigação e Desenvolvimento da Faculdade de Medicina
Portugal
EU contribution
€ 279 823,72
Address
Av. Prof. Egas Moniz
1649-028 Lisbon
Activity type
Higher or Secondary Education Establishments
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
EU contribution
€ 607 468,75
Address
Wellington Square University Offices
OX1 2JD Oxford
Activity type
Higher or Secondary Education Establishments
CENTRE HOSPITALIER UNIVERSITAIRE DE NANTES
France
EU contribution
€ 250 562,50
Address
Allee De L'ile Gloriette 5
44093 Nantes
Activity type
Higher or Secondary Education Establishments
UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS
Germany
EU contribution
€ 332 125
Address
Robert-koch-strasse 40
37075 Goettingen
Activity type
Higher or Secondary Education Establishments
CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Germany
EU contribution
€ 426 410
Address
Chariteplatz 1
10117 Berlin
Activity type
Higher or Secondary Education Establishments
AZIENDA OSPEDALIERA PAPA GIOVANNI XXIII
Italy
EU contribution
€ 298 243,75
Address
Piazza Oms 1
24127 Bergamo
Activity type
Other
ETHNIKO KAI KAPODISTRIAKO PANEPISTIMIO ATHINON
Greece
EU contribution
€ 300 000
Address
6 Christou Lada Str
10561 Athina
Activity type
Higher or Secondary Education Establishments
UNIVERSITAET LEIPZIG
Germany
EU contribution
€ 1 082 718,75
Address
Ritterstrasse 26
04109 Leipzig
Activity type
Higher or Secondary Education Establishments
ECRIN EUROPEAN CLINICAL RESEARCH INFRASTRUCTURE NETWORK
France
EU contribution
€ 306 625
Address
5 Rue Watt
75013 Paris
Activity type
Research Organisations
SOCIETE EUROPEENNE DE CARDIOLOGIE
France
EU contribution
€ 240 975
Address
Route Des Colles 2035
06903 Biot Sophia Antipolis
Activity type
Other