RECONNEXT
In 2015, the RECONNECT consortium was established, supported by CardioVasculair Onderzoek Nederland (CVON) and the Dutch Heart Foundation. RECONNECT stands for REnal CONNECTion to microvascular disease and heart failure with preserved ejection fraction (HFpEF). The results from RECONNECT made sure to provide fundamental knowledge on the connection between chronic kidney disease and HFpEF. Based on this, a translational pipeline was established for the discovery and evaluation of potential diagnostic, prognostic, and therapeutic targets, forming the basis for the next step, RECONNEXT.
The main hypothesis of the RECONNEXT consortium is:
Renal impairment and its systemic consequences adversely impact the coronary microvasculature, driving the onset and progression of HFpEF.
Role of UMCG Cardiology
Adriaan Voors has been named Clinical Trial leader of RECONNEXT and will be responsible for a Phase IIa multicenter, cross-over, double-blind, randomized, placebo-controlled trial that investigates the effects of oral geranyl geranylacetone (GGA) treatment in patients with HFpEF.
The hypothesis of the study is that GGA improves left ventricular (LV) diastolic function in patients with HFpEF by improving endothelial function and improving LV relaxation.
Patients will be treated with GGA (300 mg/day) and placebo in randomized order in two study periods of 3 months, separated by a washout period of 6 weeks. Forty patients will be recruited from the outpatient clinics of the Amsterdam University Medical Center/location VUMC, Onze Lieve Vrouwe Gasthuis, and University Medical Center Groningen.
The primary outcomes will be:
- Change in echocardiographically derived e’ between baseline and 13 weeks of treatment
- Endothelial function, measured as change in reactive hyperemia index (RHI) using peripheral applanation tonometry (EndoPAT).
The GGA-HFpEF trial is the first phase II randomized clinical trial that evaluates the effect of GGA on diastolic function, endothelial function, and kidney function in HFpEF patients. If the study shows beneficial effects of GGA, this data will form the basis for a larger, (inter)national randomized controlled multicenter trial.
