{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T12:44:26Z","timestamp":1754397866044,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:00:00Z","timestamp":1495756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL127422"],"award-info":[{"award-number":["R01HL127422"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>Mineralocorticoid receptor (<jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content>) activation plays an essential role in promoting inflammation, fibrosis, and target organ damage. Currently, no studies are investigating <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> antagonism in patients with type 2 diabetes mellitus (<jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>) with chronic kidney disease, at high risk for cardiovascular complications, who are otherwise not candidates for <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> antagonism by virtue of heart failure. Further, there is limited information on candidate therapies that may demonstrate differential benefit from this therapy. We hypothesized that <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> antagonism may provide additional protection from atherosclerosis progression in higher\u2010risk patients who otherwise may not be candidates for such a therapeutic approach. In this double\u2010blind, randomized, placebo\u2010controlled trial, subjects with <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content> with chronic kidney disease (\u2265 stage 3) will be randomized in a 1:1 manner to placebo or spironolactone (12.5 mg with eventual escalation to 25 mg daily over a 4\u2010week period). The co\u2010primary efficacy endpoint will be percentage change in total atheroma volume in thoracic aorta and left ventricular mass at 52 weeks in patients treated with spironolactone vs placebo. Secondary outcomes include 24\u2010hour mean systolic blood pressure, central aortic blood pressure, and insulin resistance (<jats:styled-content style=\"fixed-case\">HOMA\u2010IR<\/jats:styled-content>) at 6 weeks. A novel measure in the study will be changes in candidate <jats:styled-content style=\"fixed-case\">miRNAs<\/jats:styled-content> that regulate expression of <jats:italic><jats:styled-content style=\"fixed-case\">NR3C2<\/jats:styled-content><\/jats:italic> (<jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> gene) as well as measuring monocyte\/macrophage polarization in response to therapy with spironolactone. We envision that our strategy of simultaneously probing the effects of a drug combined with analysis of mechanisms of action and predictive response will likely provide key information with which to design event\u2010based trials.<\/jats:p>","DOI":"10.1002\/clc.22718","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T14:37:14Z","timestamp":1495809434000},"page":"633-640","source":"Crossref","is-referenced-by-count":8,"title":["Design of the Magnetic Resonance Imaging Evaluation of Mineralocorticoid Receptor Antagonism in Diabetic Atherosclerosis (<scp>MAGMA<\/scp>) Trial"],"prefix":"10.1002","volume":"40","author":[{"given":"Sanjay","family":"Rajagopalan","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Harrington Heart and Vascular Institute University Hospitals, Cleveland Medical Center  Ohio"},{"name":"University of Maryland School of Medicine  Baltimore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3625-717X","authenticated-orcid":false,"given":"M. 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