TESTO: Testosterone Effects on Short-Term Outcomes in Infants with XXY

项目摘要/摘要 候选人：Shanlee Davis博士是一位儿科内分泌学家，有婴儿临床和研究经验， 性染色体非整倍体的儿童和青少年。她立志成为一名国际金枪手- Klinefelter综合征(XXY)男童的肾上腺和心脏代谢功能这一奖项将促进- 在这一领域领导以患者为中心的高质量临床和转化性研究所需的技能。 背景：XXY是一种常见的遗传疾病，通过以下途径导致身体和心理社会影响- 每600个男性中就有1个人的寿命延长。XXY一直被低估、低估诊断和低估- 学习。无创性产前筛查的进步极大地提高了XXY的诊断率， 因此，迫切需要解决面临的神经发育和心脏代谢方面的挑战。 这群人。由于睾丸功能障碍，正常的婴儿睾酮(T)激增在XXY被钝化，并且 一个关键的悬而未决的问题是婴儿时期补充T的作用。然而，没有前景- 对XXY婴儿补充T的益处或副作用进行的前瞻性研究。我们假设T 治疗将在心脏代谢和神经发育结果方面产生积极的变化。 研究计划：Testo：睾酮对XXY婴儿短期结局的影响是随机的 补充T治疗XXY婴儿12周的对照交叉试验60名4至12岁的婴儿 在研究的第一个或第二个12周期间，将以1：1的随机比例接受T治疗。车身组件- 体位、神经发育、睾丸功能和安全性将在0周、12周和24周进行评估。我们会 同时，通过有针对性和无偏见的代谢组学分析，探索T对能量通路的影响。 培训：要成为一名独立的调查员，戴维斯博士需要在这两方面进行额外的培训和指导 临床和转化性研究。实现她的职业发展目标的方法将是1)经验- TIL在设计、实施和完成随机临床试验Testo和2)学术方面的培训 通过翻译科学的研讨会和完成临床研究的博士学位来接触。 环境：这个项目的环境是特殊的，有一个强大的儿科工程学术部门- 科罗拉多大学的文献学和科罗拉多CTSI的资源。非凡的儿童诊所，一家 为患有XXY的儿童提供独一无二的多学科诊所，并与家长支持团体建立关系 确保这项研究的成功招聘。在内分泌学、发育儿科方面有专长的导师- RICS、新生儿学、遗传学、代谢组学和临床研究都投资于这位候选人的未来和 将有助于支持她的研究和职业发展。 影响：这项研究的结果将影响XXY婴儿的临床护理，告知和改善神经- 发育和心脏代谢的结果。戴维斯博士将在临床试验方法方面获得宝贵的技能。 以及代谢组学，最好是作为一名临床研究人员开始有影响力的职业生涯。

PROJECT SUMMARY/ABSTRACT Candidate: Dr. Shanlee Davis is a Pediatric Endocrinologist with clinical and research experience in infants, children and adolescents with sex chromosome aneuploidies. She aspires to be an international expert in gon- adal and cardiometabolic function in boys with Klinefelter syndrome (XXY). This award will foster the develop- ment of the skills necessary to lead high-quality patient-centered clinical and translational research in this field. Background: XXY is a common genetic condition leading to physical and psychosocial implications through- out the lifespan in 1 out of every 600 males. XXY has been under-recognized, under-diagnosed, and under- studied. Advances in non-invasive prenatal screening have dramatically increased diagnosis rates of XXY, therefore there is an acute need to address the neurodevelopmental and cardiometabolic challenges facing this population. The normal infantile testosterone (T) surge is blunted in XXY due to testicular dysfunction, and a critical unanswered question is the role of T supplementation during infancy. However, there are no prospec- tive studies examining the benefits or side effects of T supplementation in XXY infants. We hypothesize that T treatment will yield positive changes in cardiometabolic and neurodevelopmental outcomes. Research Plan: TESTO: Testosterone Effects on Short-Term Outcomes in Infants with XXY is a randomized controlled cross-over trial of 12 weeks of supplemental T in infants with XXY. 60 infants between 4 and 12 weeks of age will be randomized 1:1 to receive T during the first or second 12 weeks of the study. Body com- position, neurodevelopment, testicular function, and safety will be assessed at 0, 12, and 24 weeks. We will also explore the effect of T on energy pathways using targeted and unbiased metabolomics analyses. Training: To become an independent investigator, Dr. Davis needs additional training and mentorship in both clinical and translational research. The approach to achieving her career development aims will be 1) experien- tial training in design, implementation and completion of the randomized clinical trial TESTO and 2) scholastic exposure through workshops in translational science and completion of a PhD in Clinical Investigation. Environment: The environment for this project is exceptional with a strong academic Section of Pediatric En- docrinology at the University of Colorado and resources of the Colorado CTSI. The eXtraordinarY Kids Clinic, a one-of-a-kind multidisciplinary clinic for children with XXY, and relationships with parent support groups will assure successful recruitment for this study. Mentors with expertise in endocrinology, developmental pediat- rics, neonatology, genetics, metabolomics and clinical investigation are invested in this candidate's future and will be instrumental in supporting her research and career development. Impact: The results of this study will impact the clinical care of infants with XXY, informing and improving neu- rodevelopmental and cardiometabolic outcomes. Dr. Davis will gain invaluable skills in clinical trial methodolo- gy as well as metabolomics sciences, optimally launching an impactful career as a clinical investigator.