Conditioning of the Cortisol Awakening Response in Healthy Men: Study Protocol for a Randomized Controlled Trial (Preprint)

Abstract

BACKGROUND The hormone cortisol plays important roles in human circadian and stress physiology and is an interesting target for interventions. Animal studies consistently show that cortisol is affected by pharmacological conditioning, but the results are mixed in humans. Cortisol also varies as part of a diurnal rhythm, showing a sharp increase right after awakening, the cortisol awakening response (CAR). Other studies have suggested that conditioning is also possible during sleep. OBJECTIVE We introduce a novel avenue for conditioning cortisol: by using the CAR as an unconditioned response and using scent conditioning while the participant is asleep. This study investigates an innovative way to study the effects of conditioning on cortisol and the diurnal rhythm, using a variety of devices and measures to make measurement possible at a distance and at unusual moments. METHODS The study protocol takes two weeks. Measures in week 1 are taken to reflect the CAR and waking under baseline conditions. For 3 consecutive nights in week 2, participants are exposed to a scent from 30min before awakening until their normal time of awakening. The scent thus becomes associated with the CAR. On the final night, participants are forced to wake four hours earlier, and either the same (conditioned group) or a different (control group) scent is presented half an hour before this new time. The primary outcome is the CAR, assessed by cortisol levels 0-45 minutes after awakening. Secondary outcomes are heart rate variability, actigraphy measures taken during sleep, and self-reported mood after awakening. To perform manipulations and measurements, the study uses wearable devices, online questionnaires and a programmed scent device. RESULTS Data collection is completed as of 24/12/2021. CONCLUSIONS This study can provide new insights into learning effects on cortisol and the diurnal rhythm. If the procedure does affect the CAR and associated measures, it also has potential clinical significance in the treatment of sleep and stress disorders. CLINICALTRIAL Dutch Trial register (NTR), NL58792.058.16, registered 2019-06-07