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Published in: Trials 1/2016

Open Access 01-12-2016 | Study protocol

Effects of the pattern of glucocorticoid replacement on neural processing, emotional reactivity and well-being in healthy male individuals: study protocol for a randomised controlled trial

Authors: Konstantinos Kalafatakis, Georgina M. Russell, Catherine J. Harmer, Marcus R. Munafo, Nicky Marchant, Aileen Wilson, Jonathan C. W. Brooks, Ngoc J. Thai, Stuart G. Ferguson, Kirsty Stevenson, Claire Durant, Kristin Schmidt, Stafford L. Lightman

Published in: Trials | Issue 1/2016

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Abstract

Background

Deviation from the physiological glucocorticoid dynamics (circadian and underlying ultradian rhythmicity) is a common characteristic of various neuropsychiatric and endocrine disorders as well as glucocorticoid-based therapeutics. These states may be accompanied by neuropsychiatric symptomatology, suggesting continuous dynamic glucocorticoid equilibrium is essential for brain homeostasis.

Methods/design

The study consists of two parts. The preliminary stage of the study aims to validate (technically and pharmacologically) and optimise three different patterns of systemic cortisol administration in man. These patterns are based on the combinatory administration of metyrapone, to suppress endogenous cortisol production, and concurrent hydrocortisone replacement. The second, subsequent, core part of the study is a randomised, double-blinded, placebo-controlled, crossover study, where participants (healthy male individuals aged 18–60 years) will undergo all three hydrocortisone replacement schemes. During these infusion regimes, we plan a number of neurobehavioural tests and imaging of the brain to assess neural processing, emotional reactivity and perception, mood and self-perceived well-being. The psychological tests include: ecological momentary assessment, P1vital Oxford Emotional Test Battery and Emotional Potentiated Startle Test, Leeds Sleep Evaluation Questionnaire and the visual working memory task (n-back). The neuroimaging protocol combines magnetic resonance sequences that capture data related to the functional and perfusion status of the brain.

Discussion

Results of this clinical trial are designed to evaluate the impact (with possible mechanistic insights) of different patterns of daily glucocorticoid dynamics on neural processing and reactivity related to emotional perception and mood. This evidence should contribute to the optimisation of the clinical application of glucocorticoid-based therapeutics.

Trial registration

UK Clinical Research Network, IRAS Ref: 106181, UKCRN-ID-15236 (23 October 2013)
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Metadata
Title
Effects of the pattern of glucocorticoid replacement on neural processing, emotional reactivity and well-being in healthy male individuals: study protocol for a randomised controlled trial
Authors
Konstantinos Kalafatakis
Georgina M. Russell
Catherine J. Harmer
Marcus R. Munafo
Nicky Marchant
Aileen Wilson
Jonathan C. W. Brooks
Ngoc J. Thai
Stuart G. Ferguson
Kirsty Stevenson
Claire Durant
Kristin Schmidt
Stafford L. Lightman
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1159-x

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