TRIPTORELIN FOR OVARY PROTECTION IN CHILDHOOD ONSET LUPUS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本应用的长期目标是通过治疗干预开发出保护SLE儿童性腺功能的治疗方法，其有益效果已被高质量的临床证据所证实。目前应用的预期结果是确定雷普托雷林的安全性、剂量和化疗前实现完全卵巢抑制（COS）所需的时间，并获得其对年轻SLE女性卵巢保护功效的初步证据。本应用的中心假设是，雷普妥林可以安全地实现COS，并可能有效地保护需要环磷酰胺（CYT）促性腺毒性化疗的SLE青少年女性的卵巢功能。我们基于对成年SLE 6患者的支持性研究结果提出了这一假设。这项研究的基本原理是，确定更有效的干预措施，以保持卵巢功能和避免过早绝经，将转化为提高生育能力，减少心血管疾病、骨质疏松症和其他更年期长期健康并发症的危险因素，从而降低与SLE相关的总体社会成本。在12个月的时间里，将从7个地点招募50名新需要CYT的青春期SLE女性患者，并随机接受化疗期间的雷普妥林或安慰剂。受试者的年龄约为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治疗。参与者将接受长达23个月的研究治疗。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的比例随机接受研究药物（triptorelin）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).