TRIPTORELIN FOR OVARY PROTECTION IN CHILDHOOD ONSET LUPUS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这一应用的长期目标是通过治疗干预开发保护SLE儿童性腺功能的疗法，其有益效果已被高质量的临床证据证实。目前应用的预期结果是确定曲普瑞林的安全性、其剂量和在化疗前实现完全卵巢抑制(COS)所需的时间，并获得其为患有SLE的年轻女性提供卵巢保护的初步证据。这一应用的中心假设是，曲普瑞林可以安全地实现COS，并可以有效地保护需要环磷酰胺(CyT)性腺毒性化疗的青少年女性SLE患者的卵巢功能。我们根据对成年SLE患者的支持性研究结果提出了这一假设。调查的基本原理是，找到更有效的干预措施来保护卵巢功能，避免过早绝经，将转化为生育率提高，心血管疾病、骨质疏松症和绝经后其他长期健康并发症的风险因素减少，从而降低与SLE相关的总体社会成本。在为期12个月的时间里，将从7个地点招募50名患有新近需要细胞周期疗法的SLE青少年女性，并在化疗期间随机接受曲普瑞林或安慰剂治疗。受试者的年龄大约为9-21岁，因为只有进入青春期的女性才有资格接受研究药物的治疗。参与者将接受长达23个月的学习治疗。总体研究设计为I/II期双盲安慰剂对照随机临床试验。参与者将以4：1的方式随机接受研究药物(曲普瑞林)或安慰剂(生理盐水)。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Long-term goal of this application is to develop therapies for protecting the gonadal function of children with SLE through therapeutic interventions whose beneficial effects have been verified by high-quality clinical evidence. The expected results of the current application are to determine the safety of triptorelin, its dose and the time necessary to achieve complete ovarian suppression (COS) prior to chemotherapy, as well as obtain preliminary evidence of its efficacy to provide ovarian protection for young females with SLE. The central hypothesis of this application is that triptorelin can safely achieve COS and may effectively preserve ovarian function of adolescent females with SLE requiring gonadotoxic chemotherapy with cyclophosphamide (CYT). We have formulated this hypothesis based on the results of supportive studies in adult patients with SLE 6. The rationale that underlies the investigation is that identification of more effective interventions to preserve ovarian function and avoid premature menopause will translate into increased fertility, fewer risk factors of cardiovascular disease, osteoporosis and other long-term health complications of menopause and by this lower the overall societal costs associated with SLE. Fifty adolescent females with SLE newly requiring CYT will be recruited from 7 sites over a period of 12 months and randomized to receiving during chemotherapy either triptorelin or placebo. The age of subjects will be approximately 9-21 year, as only females who have entered puberty will be eligible for treatment with the study medication. Participants will receive study treatment for up to 23 months. The general study design is a Phase I/II, double-blinded placebo controlled randomized clinical trial. Participants will be randomized in a 4:1 fashion to receive either study drug (triptorelin) or placebo (normal saline).