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: 10240281
• 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/10240281
• 关键词: Acute; Address; Adolescent; Affect; Age; Air; Award; Biological Markers; Birth; Body Composition; Body fat; Branched-Chain Amino Acids; Cardiometabolic Disease; 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; 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.

项目总结/摘要 候选人：Shanlee Davis博士是一名儿科内分泌学家，具有婴儿临床和研究经验， 性染色体非整倍性的儿童和青少年。她渴望成为一名国际专家， 患有Klinefelter综合征（XXY）的男孩的心脏和心脏代谢功能。该奖项将促进发展- 在这一领域领导高质量的以患者为中心的临床和转化研究所需的技能。 背景：XXY是一种常见的遗传性疾病，通过以下方式导致身体和心理社会影响- 每600只雄性中就有1只的寿命。XXY被低估了，诊断不足， 研究了非侵入性产前筛查的进展大大提高了XXY的诊断率， 因此，迫切需要解决神经发育和心脏代谢面临的挑战， 这个人口。由于睾丸功能障碍，正常的婴儿睾丸激素（T）激增在XXY中变钝， 一个关键的未回答的问题是婴儿期补充T的作用。然而，没有任何的prospec- 在XXY婴儿中检查T补充剂的益处或副作用的研究。我们假设T 治疗将产生心脏代谢和神经发育结果的积极变化。 研究计划：TESTO：替吉奥对XXY婴儿短期结局的影响是一项随机 在XXY婴儿中进行12周补充T的对照交叉试验。60名4至12岁的婴儿 在研究的第一周或第二个12周期间，将1：1随机分配至30周龄的受试者接受T。身体部位 将在0、12和24周时评估体位、神经发育、睾丸功能和安全性。我们将 还探讨了T对能量途径的影响，使用有针对性的和无偏见的代谢组学分析。 培训：要成为一名独立的调查员，戴维斯博士需要在这两个方面进行额外的培训和指导。 临床和转化研究。实现其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; 2）学术培训 通过转化科学研讨会和完成临床研究博士学位进行接触。 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分， 科罗拉多大学的内分泌学和科罗拉多CTSI的资源。非凡儿童诊所，a 为XXY儿童提供独一无二的多学科诊所，并与家长支持小组建立关系， 确保本研究成功招募。具有内分泌学、发育儿科学、 rics，遗传学，遗传学，代谢组学和临床研究都投资于这位候选人的未来， 将有助于支持她的研究和职业发展。 影响：本研究的结果将影响XXY婴儿的临床护理，告知和改善新生儿的营养状况。 发育和心脏代谢结果。戴维斯博士将获得宝贵的技能，在临床试验方法- 戈伊以及代谢组学科学，最佳启动作为临床研究者的影响力的职业生涯。

项目成果

Neuropsychological and mental health concerns in a multicenter clinical sample of youth with turner syndrome.

特纳综合征青少年多中心临床样本的神经心理学和心理健康问题。

• DOI: 10.1002/ajmg.a.63103
• 发表时间: 2023
• 期刊: American journal of medical genetics. Part A
• 作者: Kremen,Jessica;Davis,ShanleeM;Nahata,Leena;Kapa,HillaryM;Dattilo,TaylorM;Liu,Enju;Hutaff-Lee,Christa;Tishelman,AmyC;Crerand,CaniceE
• 通讯作者: Crerand,CaniceE

TRANSITION-RELATED DISCUSSIONS AMONG ADOLESCENT FEMALES WITH TURNER SYNDROME: CURRENT PRACTICES AND ASSOCIATED FACTORS.

患有特纳综合症的青少年女性中与过渡相关的讨论：当前实践和相关因素。

• DOI: 10.4158/ep-2020-0287
• 发表时间: 2021
• 期刊: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
• 作者: Patel,Nisha;Davis,Shanlee;Nahata,Leena
• 通讯作者: Nahata,Leena