Phase 2 Study of Theophylline for the Treatment of Psuedohypoparathyroidism

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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.