Bartholdy Savani, McClelland Jessica, Kekic Maria, O'Daly Owen G, Campbell Iain C, Werthmann Jessica, Rennalls Samantha J, Rubia Katya, David Anthony S, Glennon Danielle, Kern Nikola, Schmidt Ulrike
Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Centre for Neuroimaging Sciences, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. o.o'
Trials. 2015 Dec 3;16:548. doi: 10.1186/s13063-015-1069-3.
Anorexia nervosa (AN) is a serious mental disorder with multiple comorbidities and complications. In those with a severe and enduring form of the illness (SEED-AN), treatment responsivity is poor and the evidence base limited. Thus, there is a need for novel treatment strategies. This paper describes the theoretical background and protocol of a feasibility randomised controlled trial (RCT) of real versus sham (placebo) therapeutic repetitive transcranial magnetic stimulation (rTMS) in SEED-AN. The aim of this trial is to obtain information that will guide decision making and protocol development in relation to a future large-scale RCT of rTMS in this group of patients, and also to assess the preliminary efficacy and neural correlates of rTMS treatment.
Forty-four adults from the community with a DSM-5 diagnosis of AN, an illness duration>3 years and a previous course of unsuccessful treatment will be randomly allocated to receive 20 sessions of either real or sham rTMS, in a parallel group design. As this is a feasibility study, no primary outcome has been defined and a broad range of outcome variables will be examined. These include weight/body mass index (BMI), eating disorder psychopathology, other psychopathology (for example, depression, anxiety), quality of life, neuropsychological processes (such as self-regulation, attentional bias and food choice behaviour), neuroimaging measures (that is, changes in brain structure or function), tolerability and acceptability of rTMS, and additional service utilisation. The feasibility of conducting a large-scale RCT of rTMS and the appropriateness of rTMS as a treatment for SEED-AN will be evaluated through: assessment of recruitment and retention rates, acceptability of random allocation, blinding success (allocation concealment), completion of treatment sessions and research assessments (baseline, post-treatment and follow-up assessments). The acceptability and tolerability of the treatment will be assessed via semi-structured interviews.
The effect sizes generated and other findings from this trial will inform a future large-scale RCT with respect to decisions on primary outcome measures and other aspects of protocol development. Additionally, results from this study will provide a preliminary indication of the efficacy of rTMS treatment for AN, the neural correlates of the illness, and potential biomarkers of clinical response.
ISRCTN14329415 . Date of registration: 23 July 2015.
神经性厌食症（AN）是一种伴有多种合并症和并发症的严重精神障碍。在患有严重且持续性疾病形式（SEED-AN）的患者中，治疗反应性较差且证据基础有限。因此，需要新的治疗策略。本文描述了一项关于真实与假（安慰剂）治疗性重复经颅磁刺激（rTMS）在SEED-AN中的可行性随机对照试验（RCT）的理论背景和方案。该试验的目的是获取信息，以指导针对这组患者未来rTMS大规模RCT的决策制定和方案开发，并评估rTMS治疗的初步疗效和神经相关性。
44名来自社区、符合DSM-5诊断标准的AN成年人，病程>3年且既往治疗失败，将被随机分配接受20次真实或假rTMS治疗，采用平行组设计。由于这是一项可行性研究，未定义主要结局，将检查广泛的结局变量。这些变量包括体重/体重指数（BMI）、饮食失调精神病理学、其他精神病理学（如抑郁、焦虑）、生活质量、神经心理过程（如自我调节、注意力偏差和食物选择行为）、神经影像学测量（即脑结构或功能的变化）、rTMS的耐受性和可接受性以及额外的服务利用情况。将通过以下方面评估进行rTMS大规模RCT的可行性以及rTMS作为SEED-AN治疗方法的适用性：招募和保留率评估、随机分配的可接受性、盲法成功（分配隐藏）、治疗疗程完成情况以及研究评估（基线、治疗后和随访评估）。将通过半结构化访谈评估治疗的可接受性和耐受性。
该试验产生的效应大小和其他结果将为未来大规模RCT在主要结局测量决策和方案开发的其他方面提供信息。此外，本研究结果将初步表明rTMS治疗AN的疗效、该疾病的神经相关性以及临床反应的潜在生物标志物。
ISRCTN14329415。注册日期：2015年7月23日。
