Modified-release Hydrocortisone Therapy as a Treatment for CAH

一项为期6个月的随机第三阶段研究在122名患有经典CAH的成年人中完成，将新开发的氢化可的松(MR-HC)改良释放制剂与标准糖皮质激素进行比较。这种新开发的氢化可的松(Chronocort)配方旨在模拟正常的皮质醇昼夜节律。在NIH先前的第二阶段研究中，与基线时的传统治疗相比，6个月时的MR-HC显示全天的雄激素水平都有所改善，这种雄激素的降低是在较低或类似的每日平均糖皮质激素剂量下实现的。这导致了为期6个月的随机(MR-HC与标准糖皮质激素)国际多中心第三阶段临床试验，这是糖皮质激素治疗CAH患者的第一个随机对照试验。3期研究在6个月后未能取得初步结果，这是基于24小时的激素谱。然而，有证据表明，与标准糖皮质激素治疗相比，在700h-1500h之间对MR-HC进行更好的生化控制，并且早晨激素控制对于控制肾上腺雄激素的夜间增加是重要的。一项扩展研究正在进行中，患者报告的好处包括月经恢复和患者和伴侣怀孕。这一新的氢化可的松制剂代表了CAH患者潜在的新治疗方法。

A 6-month, randomized, Phase 3, study in 122 adults with classic CAH, comparing a newly-developed modified-release formulation of hydrocortisone (MR-HC) with standard glucocorticoid, was completed. This newly developed formulation of hydrocortisone (Chronocort) was designed to mimic the normal cortisol circadian rhythm. In a prior Phase 2 study at the NIH, compared to conventional therapy at baseline, MR-HC at 6 months showed improved androgen levels throughout the day and this lowering of androgens was achieved with a lower or similar average daily glucocorticoid dose. This led to the 6-month randomized (MR-HC vs. standard glucocorticoid) international multi-center phase 3 clinical trial, which is the first randomized, controlled trial of glucocorticoid treatment in patients with CAH. The Phase 3 study failed its primary outcome at 6 months, which was based on 24-hour hormone profiles. However, there was evidence of better biochemical control on MR-HC between 0700h-1500h compared to standard glucocorticoid therapy, and morning hormonal control is important in controlling the overnight increase in adrenal androgens. An extension study is underway with patient-reported benefits including menses restoration and patient and partner pregnancies. This novel hydrocortisone formulation represents a potential new treatment approach for patients with CAH