{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T12:17:21Z","timestamp":1779020241846,"version":"3.51.4"},"reference-count":43,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Corcept Therapeutics","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,6,17]]},"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n<jats:title>Introduction<\/jats:title>\n<jats:p>\nEven with recent treatment advances, type 2 diabetes (T2D) remains poorly controlled for many patients, despite the best efforts to adhere to therapies and lifestyle modifications. Although estimates vary, studies indicate that in &gt;10% of individuals with difficult-to-control T2D, hypercortisolism may be an underlying contributing cause. To better understand the prevalence of hypercortisolism and the impact of its treatment on T2D and associated comorbidities, we describe the two-part Hyper\n<jats:underline>\n<jats:italic>c<\/jats:italic>\n<\/jats:underline>\nortisolism in P\n<jats:italic>\n<jats:underline>at<\/jats:underline>\n<\/jats:italic>\nients with Difficult to Control Type 2 Di\n<jats:italic>\n<jats:underline>a<\/jats:underline>\n<\/jats:italic>\nbetes Despite Receiving Standard-of-Care Therapies: Preva\n<jats:italic>\n<jats:underline>l<\/jats:underline>\n<\/jats:italic>\nence and Treatment with Korl\n<jats:italic>\n<jats:underline>y<\/jats:underline>\n<\/jats:italic>\nm\n<jats:sup>\u00ae<\/jats:sup>\n(Mifepri\n<jats:italic>\n<jats:underline>st<\/jats:underline>\n<\/jats:italic>\none) (CATALYST) trial.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods and analysis<\/jats:title>\n<jats:p>\nIn part 1, approximately 1000 participants with difficult-to-control T2D (haemoglobin A1c (HbA1c) 7.5%\u201311.5% despite multiple therapies) are screened with a 1\u2009mg dexamethasone suppression test (DST). Those with post-DST cortisol &gt;1.8\u2009\u00b5g\/dL and dexamethasone level \u2265140\u2009ng\/dL are identified to have hypercortisolism (part 1 primary endpoint), have morning adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) measured and undergo a non-contrast adrenal CT scan. Those requiring evaluation for elevated ACTH are referred for care outside the study; those with ACTH and DHEAS in the range may advance to part 2, a randomised, double-blind, placebo-controlled trial to evaluate the impact of treating hypercortisolism with the competitive glucocorticoid receptor antagonist mifepristone (Korlym\n<jats:sup>\u00ae<\/jats:sup>\n). Participants are randomised 2:1 to mifepristone or placebo for 24 weeks, stratified by the presence\/absence of an abnormal adrenal CT scan. Mifepristone is dosed at 300\u2009mg once daily for 4 weeks, then 600\u2009mg daily based on tolerability and clinical improvement, with an option to increase to 900\u2009mg. The primary endpoint of part 2 assesses changes in HbA1c in participants with hypercortisolism with or without abnormal adrenal CT scan. Secondary endpoints include changes in antidiabetes medications, cortisol-related comorbidities and quality of life.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Ethics and dissemination<\/jats:title>\n<jats:p>The study has been approved by Cleveland Clinic IRB (Cleveland, Ohio, USA) and Advarra IRB (Columbia, Maryland, USA). Findings will be presented at scientific meetings and published in peer-reviewed journals.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Trial registration number<\/jats:title>\n<jats:p>\n<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial \" xlink:href=\"NCT05772169\">NCT05772169<\/jats:ext-link>\n.\n<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/bmjopen-2023-081121","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T18:31:57Z","timestamp":1721241117000},"page":"e081121","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Study protocol for a prospective, multicentre study of hypercortisolism in patients with difficult-to-control type 2 diabetes (CATALYST): prevalence and treatment with mifepristone"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct05772169","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05772169","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ralph A","family":"DeFronzo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J","family":"Auchus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9332-2524","authenticated-orcid":false,"given":"Irina","family":"Bancos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Blonde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert 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