Can Mineralocorticoid Receptor Antagonism Counteract Cardiometabolic Long-term Effects of Steroids? (MiRACCLES study)

INTERVENTION: Arm 1 ‐ oral spironolactone capsule 100mg daily for 12 weeks in a double‐blind RCT followed by an open label phase comprising treatment with oral spironolactone capsule 100mg daily x another 12 weeks CONDITION: Cardiovascular ‐ Other cardiovascular diseases Cardiometabolic complications of excess glucocorticoid exposure; ; Cardiometabolic complications of excess glucocorticoid exposure Metabolic and Endocrine ‐ Metabolic disorders PRIMARY OUTCOME: Change in total body fat mass on dual‐energy X‐ray absorptiometry (DEXA)[baseline, 12 weeks post intervention commencement (primary endpoint) and 24 weeks post intervention commencement] Change in left ventricular (LV) systolic function as assessed by global longitudinal strain (GLS) on echocardiogram[baseline, 12 weeks post intervention commencement (primary endpoint) and 24 weeks post intervention commencement] SECONDARY OUTCOME: change in fasting serum lipids[baseline, 12 weeks post intervention commencement and 24 weeks post intervention commencement] Change in insulin resistance as assessed by Homeostatic model assessment (HOMA‐IR)[baseline, 12 weeks post intervention commencement and 24 weeks post intervention commencement] change in serum HbA1C[baseline, 12 weeks post intervention commencement and 24 weeks post intervention commencement] Change in whole‐body insulin sensitivity assessed by Matsuda index from a 75‐gram oral glucose tolerance test[baseline, 12 weeks post intervention commencement and 24 weeks post intervention commencement] Changes in monocyte, dendritic cell, T cell activation markers, macrophage polarisation, phagocytosis and cytokine production assessed by flow cytometry in peripheral blood[baseline, 12 weeks post intervention commencement] Changes in myocardial strain and fibrosis estimated by integrated backscatter on echocardiogram[baseline, 12 weeks post intervention commencement and 24 weeks post intervention commencement] Changes in serum inflammatory markers (Interleukin‐6, tumour necrosis factor‐a, C‐reactive protein) measured by Enzyme‐Linked Immunosorbent Assay (ELISA)[baseline, 12 weeks post intervention commencement ] Change in diastolic function assessed by peak early diastolic velocity (Em) and the ratio of mitral inflow early diastolic velocity to peak early diastolic mitral annular velocity (E/e’) on echocardiogram[baseline, 12 weeks post intervention commencement and 24 weeks post intervention commencement] INCLUSION CRITERIA: (i) female (ii) age at least 18 years (iii) requiring glucocorticoids (GC) therapy (equivalent to at least 7.5mg/day of prednisolone average) for at least the next 3 months (iv) on nil or stable other systemic immunomodulatory drugs