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

Mills, C. E. ORCID: https://orcid.org/0000-0002-8313-3700, Govoni, V., Casagrande, M. L., Faconti, L., Webb, A. J. and Cruickshank, J. K. (2015) 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. Artery Research, 12. pp. 48-53. ISSN 18729312 doi: 10.1016/j.artres.2015.10.194

Abstract/Summary

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.