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: 9765051
• 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/9765051
• 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; 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.

项目概要/摘要 候选人： Shanlee Davis 博士是一位儿科内分泌学家，拥有婴儿临床和研究经验， 患有性染色体非整倍体的儿童和青少年。她立志成为一名国际专家 患有 Klinefelter 综合征 (XXY) 的男孩的 adal 和心脏代谢功能。该奖项将促进发展 培养在该领域领导高质量以患者为中心的临床和转化研究所需的技能。 背景：XXY 是一​​种常见的遗传病，通过以下方式对身体和心理产生影响： 每 600 名男性中就有 1 人的寿命缩短。 XXY 一直未被充分认识、诊断和诊断 研究过。无创产前筛查的进步极大地提高了 XXY、 因此，迫切需要解决所面临的神经发育和心脏代谢挑战 这个人口。由于睾丸功能障碍，正常婴儿睾酮 (T) 激增在 XXY 中减弱，并且 一个尚未解答的关键问题是婴儿期补充 T 的作用。然而，目前还没有任何前景 积极研究检查 XXY 婴儿补充 T 的益处或副作用。我们假设 T 治疗将对心脏代谢和神经发育结果产生积极的变化。 研究计划：TESTO：睾酮对 XXY 婴儿短期结果的影响是一项随机研究 对 XXY 婴儿进行 12 周补充 T 的对照交叉试验。 60 名 4 岁至 12 岁的婴儿 周龄将以 1:1 的比例随机分配，在研究的第一个或第二个 12 周期间接受 T 治疗。身体康- 将在第 0、12 和 24 周评估位置、神经发育、睾丸功能和安全性。我们将 还利用有针对性和无偏见的代谢组学分析探索 T 对能量途径的影响。 培训：要成为一名独立调查员，戴维斯博士需要在这两方面进行额外的培训和指导 临床和转化研究。实现她的职业发展目标的方法将是 1) 体验- 随机临床试验 TESTO 的设计、实施和完成方面的初步培训和 2) 学术培训 通过转化科学研讨会进行接触并完成临床研究博士学位。 环境：该项目的环境非常优越，拥有强大的儿科En-学术部门 科罗拉多大学的教义学和科罗拉多州 CTSI 的资源。非凡儿童诊所 为 XXY 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 确保本研究的成功招募。具有内分泌学、发育儿科专业知识的导师 rics、新生儿学、遗传学、代谢组学和临床研究都投资于该候选人的未来 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，告知和改善神经功能 发育和心脏代谢结果。戴维斯博士将获得临床试验方法方面的宝贵技能 gy以及代谢组学科学，以最佳方式开启作为临床研究人员的有影响力的职业生涯。