Design and progress of a factorial trial testing the effect of spironolactone and inorganic nitrate on arterial function in people at risk of or with type 2 diabetes

Background: Arterial stiffness (AS), as pulse wave velocity (PWV), is a powerful independent predictor of cardiovascular events and commonly complicates type 2 diabetes (T2D). This trial aims to test if AS, measured by the VaSera machine as cardio-ankle vascular index (CAVI) and by Arteriograph measuring central PWV, can be reduced by spironolactone and/or inorganic nitrate from beetroot juice independently of blood pressure (BP) in those with or at risk of T2D. Methods: A factorial design, double blind, randomised controlled trial in 18-80 year old men and women clinically diagnosed with T2D or at risk of it (body mass index (BMI) >= 27 kg m(-2), positive family history or glucose intolerance). The study lasts up to 36 weeks with daily intervention of either <= 50 mg spironolactone (intervention) or <= 16 mg doxazosin (control), and beetroot juice with <= 400 mg (9 mmol) inorganic nitrate (intervention) or placebo beetroot juice, 0 mg nitrate (control). Non-invasive AS measurements are carried out at baseline and then at 12-week intervals thereafter. Results: To date, 95 participants have been consented and screened, 19 of these were not suitable or not willing to participate so that 73 have been randomised with 9 participants screened as eligible and awaiting randomisation. 53 participants have completed the study. Mean baseline and follow up measures of cardiac-ankle and cardiac-aortic bifurcation PWV and BP have been straightforward. Conclusion: This is a proof-of-principle trial to alter AS independent of BP in a patient sample at high cardiovascular risk. Clinical trial registration information: UK Clinical Research Network Portfolio Database: 25003627. (C) 2015 Association for Research into Arterial Structure and Physiology. Published by Elsevier B.V. All rights reserved.