Phase 2 Study of Theophylline for the Treatment of Psuedohypoparathyroidism

茶碱治疗假性甲状旁腺功能减退症的 2 期研究

• 批准号: 10775196
• 负责人: Ashley Hall Shoemaker
• 金额: $ 21.64万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-24 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10775196
• 关键词: Academic Medical Centers; Age; Award; Body Weight decreased; Body mass index; Categories; Child; Childhood; Clinic; Clinical Research; Clinical Trials; Complement; Continuous Glucose Monitor; Data; Development; Environment; Ethnic Origin; Evaluation; Exercise Tolerance; Funding; Future; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; Gender; General Population; Genetic Diseases; Glucose; Glucose tolerance test; Goals; Grant; Heterozygote; Human Subject Research; Hyperglycemia; Impaired cognition; Impairment; Individual; Infrastructure; Insulin; Insulin Resistance; Learning; Life; Light; Manuscripts; Master of Science; Measurement; Measures; Mentors; Mentorship; Metabolic; Metabolism; Monitor; Mutation; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Obstructive Sleep Apnea; Parents; Participant; Physical activity; Physicians; Population; Population Decreases; Positioning Attribute; Prediabetes syndrome; Pseudohypoparathyroidism; Race; Rare Diseases; Research; Research Personnel; Research Training; Resources; Risk; Scientist; Signal Transduction; Site; Sleep; Sleep Disorders; Techniques; Technology; Testing; Theophylline; Time; Training; Translational Research; Travel; United States National Institutes of Health; Walking; Writing; actigraphy; career; career development; clinical investigation; cohort; early-onset obesity; exercise capacity; gene repression; glucose tolerance; hormone resistance; improved; insight; metabolic abnormality assessment; monitoring device; patient oriented; phase 2 study; poor sleep; primary outcome; remote assessment; remote monitoring; responsible research conduct; secondary outcome; sedentary; skills; sleep pattern; tool; training opportunity; wearable device; young adult

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.

项目摘要 假型甲状旁腺功能减退1A（PHP1A）是一种罕见的遗传疾病，由刺激性受损引起 G蛋白（GSα）信号通过基因GNA的下调。 PHP1A导致多激素 阻力和早期对象。家长R01（PI：Shoemaker，R01DK118407）正在评估是否是否 phylline降低了体重指数，并提高了PHP1A中的葡萄糖耐受性。作为此临床的一部分 试验，正在评估口服葡萄糖耐受性测试和6分钟的步行测试以评估糖血症，胰岛素 阻力和活动。 这项补充研究的总体科学目标是评估血糖，活动和睡眠 使用远程可穿戴技术，包括连续葡萄糖监测器（CGM）和Actiography。主要 这项研究的目的是比较CGM上高血糖的百分比，通过行为摄影和 PHP1A和匹配对照的个体中通过行动摄影的睡眠持续时间。次要结果将 通过研究评估（包括OGTT和6分钟步行测试）评估这些“现实世界”参数。 这项研究的总体职业发展目标是提供全面的培训 使申请人能够通过临床和翻译研究成为独立的身体科学家 专注于胰岛素抵抗和血糖症的职业。申请人将学习人类学科的关键技能 通过完成这项研究的完成和临床研究理学硕士的研究。她会的 扩展她对代谢参数的理解，学会利用临床中的远程监控设备 研究，并在人类受试者的罕见疾病研究中获得专业知识。这个专家和教学 学习将与持续的专业发展，赠款写作，手稿写作以及 负责任的研究培训。申请人的主要导师Ashley Shoemaker博士和 Menorship Team是葡萄糖和胰岛素代谢的专家，活动评估和临床研究 在罕见疾病中。他们已经在NIH F32上提供了适用的杰出精神制。 奖项（F32DK128970，2021年8月）。范德比尔特大学医学中心（VUMC）提供了出色的 研究环境，为年轻的研究人员提供丰富的资源和培训机会。