背景:多囊卵巢综合征(PCOS)是最普遍的,青少年和年轻女性的慢性内分泌代谢紊乱(AYAs),影响全球5-10%的AYAs。没有批准的PCOS药物治疗。口服避孕药(OC)的标准标签外治疗既不能恢复潜在的病理生理学,也不能恢复相关的合并症。试点研究对PCOS的发病机制产生了新的见解,导致开发一种新的治疗方法,两种所谓的胰岛素致敏剂的低剂量组合[吡格列酮(PIO),二甲双胍(MET)]和一种混合的抗雄激素和抗盐皮质激素也可作为棕色脂肪组织的激活剂[螺内酯(SPI)],在一个单一的片剂(SPIOMET)。本试验将评估疗效,SPIOMET的耐受性和安全性,在生活方式衡量标准之上,用于治疗AYAs中的PCOS。
方法:在这个多中心中,随机化,双盲,安慰剂对照,四臂,平行组,II期临床试验,与PCOS的AYAs将从欧洲的7个临床中心招募。意图是将总共364名符合条件的患者随机分为四个组(1:1:1:1):安慰剂,PIO,SPI+PIO(SPIO)和SPI+PIO+MET(SPIOMET)。超过12个月的积极治疗将包括生活方式指导以及每天(在晚餐时间)摄入一片;治疗后的随访将持续6个月。主要终点是治疗前后的排卵率。次要终点是临床特征(多毛症,月经规律);内分泌代谢变量(雄激素,脂质,胰岛素,炎症标志物);表观遗传标志物;影像学数据(颈动脉内膜中层厚度,身体成分,腹部脂肪分割,肝脂肪);安全性;依从性,药物的耐受性和可接受性;以及研究参与者的生活质量。SPIOMET的优势(按这个顺序),SPIO和PIO将在安慰剂上进行测试,如果存在,随后SPIOMET与PIO的优势,如果仍然存在,最后是SPIO。
结论:本研究将是第一个在随机,双盲,安慰剂对照的方式-疗效,SPIOMET治疗早期PCOS的耐受性和安全性,在生活方式干预之上。
背景:EudraCT2021-003177-58。2021年12月22日注册。https://www.临床试验登记。欧盟/ctr搜索/搜索?查询=%092021-003177-58。
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5-10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs.
METHODS: In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO.
CONCLUSIONS: The present study will be the first to evaluate-in a randomised, double-blind, placebo-controlled way-the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention.
BACKGROUND: EudraCT 2021-003177-58. Registered on 22 December 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58 .