Effects of modified release hydrocortisone on restoration of early morning cortisol, quality of life, and fatigue in adrenal insufficiency (The CHAMPAIN study): a randomised, double-blind, double-dummy, cross-over study comparing Chronocort and Plenadren

作者：Alessandro Prete, Verena Theiler‐Schwetz, Wiebke Arlt, Jon Hazeldine, Irina-Oana Chifu, Birgit Harbeck, Catherine Napier, John D C Newell-Price, D Aled Rees, Nicole Reisch, Günter Karl Stalla, Helen Coope, Kerry Maltby, John Porter, Jo Quirke, R. J. M. Ross · 发表于：EClinicalMedicine · 年份：2026 · DOI：10.1016/j.eclinm.2025.103714 · 被引用次数：6 · 研究领域：Adrenal Hormones and Disorders、Stress Responses and Cortisol、Hormonal Regulation and Hypertension

Background: Cortisol has a circadian rhythm with an early morning rise, loss of this rhythm is associated with poor health. Our objective was to test the hypothesis that restoring the early morning cortisol rise will improve fatigue and quality of life (QoL) by comparing twice daily Chronocort with once daily Plenadren in patients with adrenal insufficiency. Methods: A randomised, double-blind, double-dummy, cross-over study with no washout in 58 patients (29 in each arm) with primary adrenal insufficiency comparing four weeks' Chronocort, 15 mg at night and 10 mg in the morning, a formulation that restores early morning cortisol levels, with four weeks' once daily Plenadren 25 mg, which only restores daytime cortisol levels. The primary endpoint was the 07:00 h serum cortisol level and secondary endpoints measures of fatigue and QoL. The trial was registered on ClinicalTrials.gov and EU Clinical Trials Register (NCT NCT05222152; Eudract 2021-000144-21), initiated on 11th January 2022 and completed on 18th October 2023. Findings: Patients met the primary endpoint and achieved a physiological early morning serum cortisol, median 417 nmol/L on Chronocort versus 6 nmol/L on Plenadren (P < 0.0001). For secondary outcomes the majority of QoL and fatigue measures showed significant benefits for Chronocort including the disease-specific questionnaire AddiQol (P = 0.02), the fatigue questionnaire PROMIS 7b (P = 0.02), SF-36 physical component score (P = 0.01), and EQ-5D-5L (P = 0.02)...