Skip to main content
ENDO 2026 Main banner

Adrenal (Excluding Mineralocorticoids)

MON-487 - Replacing Early Morning Cortisol Reduces Fatigue in Patients with Adrenal Insufficiency: Post-Hoc Analysis of CHAMPAIN, A Double-Blind Study Comparing Chronocort and Plenadren

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Richard John M Ross, MBBS,FRCP,MD: Neurocrine: Consultant ()
Wiebke Arlt, MD DSc FRCP FMedSci: No financial relationships to disclose
John Newell-Price, MD, PhD, FRCP: Crinetics: Advisory Board (); recordati: Writing commitee (); Sparrow Therapeutics: Grant Recipient ()
Aled Rees, MD,PhD: Diurnal Ltd: Advisory Board (); Immedica Pharma AB: Honorarium Recipient (); Neurocrine Biosciences: Advisory Board (), Contracted Research (Principal Investigators must provide information, even if received by the institution) (), Honorarium Recipient (); Recordati Rare Disease: Advisory Board ()


Background: Cortisol has a circadian rhythm with an early morning rise, loss of this rhythm is associated with poor health. In the CHAMPAIN study we demonstrated that twice daily Chronocort (Efmody, Immedica Netherlands B.V.), which replaces the early morning rise in cortisol, improved QoL compared to Plenadren (Takeda Ltd. UK), which only replaces daytime cortisol levels. This post-hoc analysis looked at the sub-domains of the disease specific questionnaire, AddiQoL (Addison's disease Quality of Life questionnaire) and SF-36 V2, compared to other questionnaires.

Methods: CHAMPAIN was a double-blind cross-over study in 58 patients with primary adrenal insufficiency (AI) comparing Chronocort, 15mg at night and 10mg in the morning, with once daily Plenadren 25mg. The primary endpoint was waking cortisol and secondary endpoints were measures of fatigue and QoL. Patients signed informed consent and the trial was registered (NCT NCT05222152; Eudract 2021-000144-21). AddiQoL has four subdomains: fatigue, emotions, symptoms, and miscellaneous and was completed every 4 weeks within 2 hours of waking. A sensitivity analysis was done on period 1 of the cross-over which was randomized parallel-arm and blinded. P was one-sided, significance at P< 0.025.

Results: In the cross-over analysis treatment effect was in favor of Chronocort for AddiQoL: Total Score (+3.214, P=0.024), and subdomain Fatigue (+1.234, P=0.014), but not different for Emotions (+0.861, P=0.032), Symptoms (+0.500, P=0.157) and miscellaneous (+0.676, P=0.033). In the sensitivity analysis Total Score was positive (+6.3, P=0.0175). The SF-36 V2 physical component score which includes fatigue was in favor of Chronocort (+3.2, P=0.01) but the Mental Component Score was not different (-0.6 P=0.7). In the sensitivity analysis the following SF-36 subdomains significantly favored Chronocort: Physical Functioning (+5.42 P=0.004), Role Limitations due to Physical Health (+7.59 P=0.001), Bodily Pain (+4.99 P=0.022), General Health Perceptions (+5.70 P=0.004), and Vitality (+7.16 P=0.002). The PROMIS 7b, a specific fatigue questionnaire, was in favor of Chronocort (-2.6, P=0.024). The most common adverse event was fatigue, reported by twice as many during Plenadren treatment (44.6%) compared to Chronocort (20.7%).

Conclusions: Replacing the early morning cortisol improved health related QoL in AI based on the disease specific questionnaire AddiQoL. This was primarily due to reduced fatigue which was also seen in the SF-36 physical component score and fatigue specific questionnaire PROMIS 7b and there were fewer reports of fatigue on Chronocort compared to Plenadren.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*