Federal Project Grant Award Summary

Mayo Clinic received a $741,387 Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), effective February 20, 2026, with completion anticipated December 31, 2030. The award funds a randomized, double-blinded, placebo-controlled clinical trial investigating overnight metyrapone intervention in patients with Mild Autonomous Cortisol Secretion (MACS), a condition affecting 1-2% of the adult population and associated with elevated cardiovascular morbidity and mortality. The research will evaluate the safety, tolerance, and efficacy of metyrapone therapy over a 12-month treatment period while examining its impact on adrenal steroid metabolism, circadian cortisol secretion patterns, metabolic outcomes, and frailty markers.

The deliverables encompass three primary research objectives: determining safety and tolerance of overnight metyrapone administration; assessing impacts on adrenal steroid metabolome and circadian cortisol secretion normalization; and evaluating metabolic outcomes, frailty reversal, and exploratory outcomes including cognition and senescence biomarkers. This clinical research initiative directly supports NIDDK's programmatic focus on fundamental and clinical studies addressing the etiology, pathogenesis, prevention, diagnosis, and treatment of endocrine and metabolic diseases, with the overarching goal of demonstrating whether adverse health outcomes associated with MACS are reversible through targeted therapeutic intervention.