A Single-Center Prospective Natural History Study of RYR1-Related Disorders


Clinical Trials

Poster Number: V416


Irene Chrismer, RN, BSN, CCRP, National Institutes of Health, Joshua Todd, Phd, NINDS/DIR/CNP/OCD, Tokunbor Lawal, PhD, FNP-BC, National Institutes of Health

Institutional Review Board approval has recently been granted for this prospective natural history study. The primary objective of this observational study is to characterize the clinical manifestations and course of ryanodine receptor 1-related disorders (RYR1-RD) in both children and adults. We plan to enroll a total of 75 adults and 75 children (>7 years of age), for a total of 150 participants. The study comprises a primary data collection phase (Years 1-3) and extended follow-up phase (Years 4-5).

In order to include individuals of all physical abilities, participants will be enrolled in either a centralized or decentralized arm. During each phase, participants in the centralized arm will visit the National Institute of Health (NIH), in Bethesda MD, once per year, while those in the decentralized cohort will be seen annually via telehealth. Participants in the centralized cohort will complete a series of assessments including physical examinations, pulmonary function tests, ophthalmological examinations, fatigue and quality of life questionnaires, laboratory tests, exercise and physical therapy evaluations, muscle imaging, and accelerometry. Participants in the decentralized cohort will undergo physical examinations, questionnaires, laboratory tests, and accelerometry.

Laboratory testing will include exploratory biomarkers, such as NAD+, NADH, GSH, GSSG, 15-F2t isoprostane, and CPK. These biomarkers will provide valuable insights into the underlying mechanisms of RYR1-RD.

In addition to characterizing the phenotype and disease course over a total of five years, this study aims to contribute to the existing knowledge of RYR1-RD and support clinical trial readiness in this heterogenous group of disorders.