Phase 2 Study of Theophylline for the Treatment of Psuedohypoparathyroidism

项目摘要 假性甲状旁腺功能减退1A型（PHP1A）是一种罕见的遗传性疾病，由受损的刺激性 G蛋白（Gsα）通过下调基因GNAS进行信号传导。PHP1A导致多激素 抵抗力和早发性肥胖。父R01（PI：Shoemaker，R01DK118407）正在评估是否 茶碱降低PHP1A的体重指数并改善葡萄糖耐量。在本次临床 一项试验，口服葡萄糖耐量试验和6分钟步行试验正在进行评估，以评估胰岛素， 阻力和活动。 这项补充研究的首要科学目标是评估睡眠，活动和睡眠 使用远程可穿戴技术，包括连续葡萄糖监测仪（CGM）和活动记录仪。主 本研究的目的是比较CGM上的高血糖百分比，通过体动记录仪进行的体力活动， PHP1A患者和对照组通过体动记录仪记录的睡眠持续时间。次要结局将 通过OGTT和6分钟步行试验等研究评估来评估这些“真实世界”参数。 这项研究的总体职业发展目标是提供全面的培训， 使申请人成为一名独立的医生，科学家与临床和转化研究 主要研究胰岛素抵抗和糖尿病。申请人将学习人类受试者的关键技能。 通过完成这项研究和临床研究理学硕士研究。她将 扩展她对代谢参数的理解，学习在临床中使用远程监测设备 研究，并获得人类受试者在罕见疾病研究方面的专业知识。这种经验和说教 学习将与持续的专业发展，赠款写作，手稿写作， 培训负责任的研究行为。申请人的主要导师，阿什利舒梅克博士， 导师团队是葡萄糖和胰岛素代谢，活动评估和临床研究方面的专家 在罕见疾病中。到目前为止，他们为申请人提供了特殊的指导，而在NIH F32 奖项（F32DK128970，2021年8月）。范德比尔特大学医学中心（VUMC）提供了一个杰出的 为年轻研究人员提供丰富的资源和培训机会。

PROJECT SUMMARY Pseudohypoparathyroidism type 1A (PHP1A) is a rare, genetic disorder caused by impaired stimulatory G protein (Gsα) signaling through downregulation of the gene, GNAS. PHP1A results in multi-hormone resistance and early-onset obesity. The parent R01 (PI: Shoemaker, R01DK118407) is evaluating whether theophylline decreases body mass index and improves glucose tolerance in PHP1A. As part of this clinical trial, oral glucose tolerance tests and 6-minute walk tests are being evaluated to assess glycemia, insulin resistance, and activity. The overarching scientific goal of this supplemental study is to evaluate glycemia, activity, and sleep using remote, wearable technology including continuous glucose monitors (CGM) and actigraphy. The primary objectives of this study are to compare percent hyperglycemia on CGM, physical activity via actigraphy, and sleep duration via actigraphy in individuals with PHP1A and matched controls. Secondary outcomes will evaluate these “real-world” parameters with study assessments including OGTT and 6-minute walk tests. The overarching career development goal of this study is to provide comprehensive training that will enable the applicant to become an independent physician-scientist with a clinical and translational research career focusing on insulin resistance and dysglycemia. The applicant will learn critical skills in human subjects’ research through both the completion of this study and the Master of Science in Clinical Investigation. She will extend her understanding of metabolic parameters, learn to utilize remote monitoring devices in clinical research, and gain expertise in human subjects’ research in rare diseases. This experiential and didactic learning will be in conjunction with continued professional development, grant writing, manuscript writing, and training in responsible conduct of research. The applicant’s primary mentor, Dr. Ashley Shoemaker, and mentorship team are experts in glucose and insulin metabolism, the evaluation of activity, and clinical research in rare diseases. They have provided the applicant exceptional mentorship thus far, while on the NIH F32 award (F32DK128970, August 2021). Vanderbilt University Medical Center (VUMC) provides an outstanding research environment with abundant resources and training opportunities for young investigators.