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

TESTO：睾酮对 XXY 婴儿短期结果的影响

• 批准号: 10002042
• 负责人: Shanlee Davis
• 金额: $ 16.52万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002042
• 关键词: Acute; Address; Adolescent; Affect; Age; Air; Award; Biological Markers; Birth; Body Composition; Body fat; Branched-Chain Amino Acids; Cardiovascular Diseases; Cause of Death; Cell physiology; Child; Childhood; Chromosome abnormality; Clinic; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Cognitive; Colorado; Cross-Over Trials; Data; Development; Diagnosis; Disease; Doctor of Philosophy; Dose; Educational workshop; Endocrinologist; Endocrinology; Energy Metabolism; Environment; Epigenetic Process; Equipoise; Failure; Fostering; Functional disorder; Future; Gene Dosage; Genetic; Genetic Diseases; Gonadal Steroid Hormones; Gonadotropins; Growth; Health; Hormones; Individual; Infant; Infant Care; Insulin; International; Intervention; Intramuscular Injections; Karyotype; Klinefelter' s Syndrome; Language; Lead; Leptin; Life; Lipids; Longevity; Measures; Mentors; Mentorship; Metabolic; Metabolic dysfunction; Mitochondria; Modification; Monitor; Motor Skills; Neonatology; Neurocognition; Neurocognitive Deficit; Outcome; Parents; Pathway interactions; Pediatrics; Phenotype; Pilot Projects; Placebos; Play; Plethysmography; Population; Prospective Studies; Puberty; Randomized; Randomized Clinical Trials; Reporting; Research; Research Personnel; Research Support; Resources; Role; Safety; Science; Serum; Standardization; Supplementation; Support Groups; Surrogate Markers; Testing; Testosterone; Time; Training; Translational Research; Universities; Work; X Chromosome; acylcarnitine; adverse outcome; base; boys; cardiometabolism; career; career development; clinical care; clinical investigation; clinical practice; design; efficacy study; evidence base; experience; gonad function; hypothalamic pituitary gonadal axis; improved; infancy; male; men; metabolomics; mortality; motor deficit; multidisciplinary; neurodevelopment; patient oriented; prenatal testing; primary outcome; psychosocial; recruit; research and development; safety outcomes; secondary outcome; sertoli cell; sex chromosome aneuploidy; side effect; skill acquisition; skills; standard of care; treatment arm

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.

项目摘要/摘要 候选人：Shanlee Davis博士是一名儿科内分泌学家，在婴儿中具有临床和研究经验， 具有性染色体非整倍性的儿童和青少年。她渴望成为GON的国际专家 KlineFelter综合征（XXY）男孩中的ADAL和心脏代谢功能。该奖项将促进发展 - 在该领域领导以患者为中心的临床和转化研究所需的技能。 背景：XXY是一种常见的遗传条件，导致身体和心理社会意义 每600名男性中有1个寿命。 XXY的公认，未经诊断和未诊断不足 研究。非侵入性产前筛查的进步显着提高了XXY的诊断率， 因此，急需应对神经发育和心脏代谢挑战 这个人口。正常婴儿睾丸激素（T）激增因睾丸功能障碍而在XXY中钝化，并且 一个关键的未解决问题是补充在婴儿期间的作用。但是，没有 研究XXY婴儿中T补充T的益处或副作用的研究。我们假设T 治疗将导致心脏代谢和神经发育结果的正变化。 研究计划：Testo：睾丸激素对XXY婴儿短期结局的影响是一个随机的 XXY婴儿的12周补充T的控制跨界试验。 40名4至12岁的婴儿 在研究的第一个或第二个12周中，几周的年龄将被随机分配为1：1。身体 位置，神经发育，睾丸功能和安全性将在0、12和24周评估。我们将 还使用靶向和无偏的代谢组学分析探索T对t对能量途径的影响。 培训：要成为一名独立研究者，戴维斯博士都需要在这两个方面进行其他培训和指导 临床和翻译研究。实现她的职业发展目标的方法将是1）体验 - 在设计，实施和完成随机临床试验测试和2）Scholastic方面的设计，实施和完成培训 通过转化科学讲习班的接触和临床研究中的博士学位完成。 环境：该项目的环境非常出色，有很强的小儿学术部分 科罗拉多大学的Docrinology和科罗拉多州CTSI的资源。非凡的儿童诊所 XXY儿童的独一无二的多学科诊所以及与父母支持小组的关系 确保这项研究成功招募。具有内分泌学专业知识，发育典范方面的专业知识的导师 - RIC，新生儿学，遗传学，代谢组学和临床研究投入了该候选人的未来和 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，向Neu-neu- 竞技和心脏代谢结果。戴维斯博士将获得临床试验方法的宝贵技能 - GY和代谢组学科学，最佳地从事临床研究者的影响力。