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.
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.
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DOI：
10.1186/s13063-016-1159-x
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发表时间：
2016-01-22
期刊：
影响因子：
2.5
通讯作者：
Lightman SL
中科院分区：
文献类型：
--
作者：
Kalafatakis K;Russell GM;Harmer CJ;Munafo MR;Marchant N;Wilson A;Brooks JC;Thai NJ;Ferguson SG;Stevenson K;Durant C;Schmidt K;Lightman SL
偏离生理糖皮质激素动力学(昼夜节律和潜在的超常节律性)是各种神经精神和内分泌疾病以及以糖皮质激素为基础的治疗的共同特征。这些状态可能伴随着神经精神症状，提示持续的动态糖皮质激素平衡对大脑稳态是必不可少的。本研究由两部分组成。该研究的初步阶段旨在验证和优化人体内三种不同的全身性皮质醇给药模式(技术和药理学上)。这些模式是基于联合应用美替拉酮，以抑制内源性皮质醇的产生，以及同时使用氢化可的松替代。这项研究的第二个核心部分是随机、双盲、安慰剂对照的交叉研究，参与者(18-60岁的健康男性个体)将接受所有三种氢化可的松替代方案。在这些输液过程中，我们计划进行一些神经行为测试和大脑成像，以评估神经处理、情绪反应和知觉、情绪和自我感知的幸福感。心理测试包括：生态瞬间评估、P1VITAL牛津情绪测试组合和情绪强化惊吓测试、利兹睡眠评估问卷和视觉工作记忆任务(n-back)。神经成像方案结合了磁共振序列，这些序列捕获与大脑功能和血流状态相关的数据。这项临床试验的结果旨在评估每日糖皮质激素动态的不同模式对与情绪感知和情绪相关的神经处理和反应性的影响(可能有机制上的见解)。这一证据应该有助于优化以糖皮质激素为基础的治疗的临床应用。英国临床研究网络，IRAS参考文献：106181，UKCRN-ID-15236(2013年10月23日)
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. 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. 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. UK Clinical Research Network, IRAS Ref: 106181, UKCRN-ID-15236 (23 October 2013)