University of Texas Health Science Center, San Antonio, Texas, USA.
Departments of Pharmacology and Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Ann Arbor, Michigan, USA.
BMJ Open. 2024 Jul 16;14(7):e081121. doi: 10.1136/bmjopen-2023-081121.
Even 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 >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 ortisolism in P ients with Difficult to Control Type 2 Di betes Despite Receiving Standard-of-Care Therapies: Preva ence and Treatment with Korl m (Mifepri one) (CATALYST) trial.
In part 1, approximately 1000 participants with difficult-to-control T2D (haemoglobin A1c (HbA1c) 7.5%-11.5% despite multiple therapies) are screened with a 1 mg dexamethasone suppression test (DST). Those with post-DST cortisol >1.8 µg/dL and dexamethasone level ≥140 ng/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). 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 mg once daily for 4 weeks, then 600 mg daily based on tolerability and clinical improvement, with an option to increase to 900 mg. 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.
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.
NCT05772169.
尽管最近有了治疗进展，但许多患者的 2 型糖尿病（T2D）仍控制不佳，尽管他们尽力坚持治疗和生活方式改变。尽管估计有所不同，但研究表明，在难以控制的 T2D 患者中，超过 10%的患者可能存在皮质醇过多症，这是导致疾病的一个潜在原因。为了更好地了解皮质醇过多症的患病率以及其治疗对 T2D 及其相关合并症的影响，我们描述了接受标准治疗的 2 型糖尿病患者中皮质醇过多症的两项研究：接受 Korl m（米非司酮）治疗的困难控制型 2 型糖尿病患者中的皮质醇过多症患病率和治疗（CATALYST）试验。
在第 1 部分中，大约 1000 名难以控制的 T2D 患者（糖化血红蛋白（HbA1c）在 7.5%-11.5%，尽管使用了多种治疗方法）接受了 1mg 地塞米松抑制试验（DST）的筛查。那些在 DST 后皮质醇>1.8μg/dL 和地塞米松水平≥140ng/dL 的患者被确定为皮质醇过多症（第 1 部分主要终点），他们的早晨促肾上腺皮质激素（ACTH）和脱氢表雄酮硫酸盐（DHEAS）水平会被测量，并接受非对比性肾上腺 CT 扫描。需要评估升高的 ACTH 的患者会被转介到研究之外进行治疗；那些 ACTH 和 DHEAS 水平在正常范围内的患者可能会进入第 2 部分，这是一项随机、双盲、安慰剂对照试验，评估使用竞争性糖皮质激素受体拮抗剂米非司酮（Korlym）治疗皮质醇过多症的效果。参与者按照 2:1 的比例随机分配接受米非司酮或安慰剂治疗 24 周，按是否存在异常肾上腺 CT 扫描进行分层。米非司酮的剂量为 300mg 每日一次，持续 4 周，然后根据耐受性和临床改善情况，每日剂量增加至 600mg，如果需要，可以增加至 900mg。第 2 部分的主要终点是评估有或无异常肾上腺 CT 扫描的皮质醇过多症患者的 HbA1c 变化。次要终点包括抗糖尿病药物的变化、与皮质醇相关的合并症和生活质量。
该研究已获得克利夫兰诊所机构审查委员会（克利夫兰，俄亥俄州，美国）和 Advarra 机构审查委员会（马里兰州哥伦比亚，美国）的批准。研究结果将在科学会议上公布，并发表在同行评议的期刊上。
NCT05772169。
