Study of a corticotropin releasing factor-1 receptor antagonist for the treatment of congenital adrenal hyperplasia

促肾上腺皮质激素释放因子1受体拮抗剂治疗先天性肾上腺皮质增生症的研究

• 批准号: 10916863
• 负责人: Deborah Merke
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10916863
• 关键词: Adrenal Glands; Adrenal hormone preparation; Affinity; Androgens; Biological Markers; CRF receptor type 1; Chronic; Clinical Research; Congenital adrenal hyperplasia; Corticotropin; Corticotropin-Releasing Hormone; Development; Disease; Dose; Double-Blind Method; Functional disorder; Glucocorticoids; Hypothalamic structure; Investigation; Minor; Patients; Phase; Pituitary Gland; Production; Randomized; Safety; adverse outcome; alternative treatment; antagonist; disorder control; healthy volunteer; novel therapeutics; phase 2 study; placebo controlled study; receptor; safety study; small molecule

Excess glucocorticoid therapy is often needed to control the overproduction of adrenal androgens in congenital adrenal hyperplasia. High-affinity and selective small-molecule antagonists of CRF type 1 receptors in the pituitary gland are in development and might allow for lower glucocorticoid therapy. The mechanism of action has been validated in a previous proof-of-concept study and has been shown to be safe in Phase 1 clinical studies in healthy volunteers and Phase 2 dose finding studies of patients with CAH. In Phase 2 studies, patients with poor disease control at baseline had reductions in biomarkers; while patients with good disease control at baseline showed only minor changes. A randomized, double-blind, placebo-controlled study is underway which will explore the safety and efficacy of CRF type 1 receptor antagonist. This study represents the investigation of a novel therapy in the treatment of congenital adrenal hyperplasia.

在先天性肾上腺皮质增生症中，通常需要过量糖皮质激素治疗来控制肾上腺雄激素的过度产生。垂体中CRF 1型受体的高亲和力和选择性小分子拮抗剂正在开发中，可能允许较低的糖皮质激素治疗。作用机制已在先前的概念验证研究中得到验证，并已在健康志愿者的I期临床研究和CAH患者的II期剂量探索研究中证明是安全的。在II期研究中，基线时疾病控制不佳的患者生物标志物减少;而基线时疾病控制良好的患者仅显示轻微变化。 一项随机、双盲、安慰剂对照研究正在进行中，该研究将探索CRF 1型受体拮抗剂的安全性和疗效。这项研究代表了一种新的治疗先天性肾上腺皮质增生症的治疗方法的调查。