Clinical outcomes and neural correlates of 20 sessions of repetitive transcranial magnetic stimulation in severe and enduring anorexia nervosa (the TIARA study): study protocol for a randomised controlled feasibility trial

Abstract

BackgroundAnorexia 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.DesignForty-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.DiscussionThe 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.Trial registrationISRCTN14329415. Date of registration: 23 July 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-1069-3) contains supplementary material, which is available to authorized users.

A systematic review of the relationship between eating, weight and inhibitory control using the stop signal task

“…These include non-invasive computerised paradigms, such as attentional bias modification protocols (Boutelle et al, 2014;Kemps et al, 2014;Renwick et al, 2013), that experimentally manipulate changes in attentional processes to manipulate eating behaviour. In addition, the potential of brain stimulation techniques that can alter the activity of specified brain regions is under investigation (Bartholdy et al, 2015a;Bartholdy et al, 2013;Bou Khalil and El Hachem, 2014;Schmidt and Campbell, 2013;Truong et al, 2013;Val-Laillet et al, 2015). These neuromodulation techniques show promise in treating both symptoms and food craving (Kekic et al, 2014), EDs (Khedr et al, 2014;Lipsman et al, 2013;McClelland et al, 2013a;McClelland et al, 2013b;McClelland et al, 2015;Pires Baczynski et al, 2014;Van den Eynde et al, 2011a;Van den Eynde et al, 2010;Van den Eynde et al, 2013) and overweight or obesity (Frank et al, 2012;Gluck et al, 2015;Montenegro et al, 2012).…”

Labeling and defining severe and enduring anorexia nervosa: A systematic review and critical analysis

“…Does the treatment need to be evidence‐based or can any type of treatment be deemed appropriate? Despite some authors providing some indication as to what constitutes an adequate treatment option (Bamford & Mountford, ; Lipsman et al, ; Marrazzi & Luby, ; Saeidi et al, ; Wang et al, ), others do not (Bartholody et al, ; Geller et al, ; Hay & Touyz, ; Mander, Teufel, Keifenheim, Zipfel, & Giel, ). With treatment options for AN being broad and most likely only to broaden, these questions need to be examined and the answers made explicitly clear if it is to be used in a future definition.…”

“…Does the treatment need to be evidence-based or can any type of treatment be deemed appropriate? Despite some authors providing some indication as to what constitutes an adequate treatment option (Bamford & Mountford, 2012;Lipsman et al, 2013;Marrazzi & Luby, 1986;Saeidi et al, 2013;Wang et al, 2013), others do not (Bartholody et al, 2015;Geller et al, 2001;Mander, Teufel, Keifenheim, Zipfel, & Giel, 2013).…”

Contemporary views on the genetics of anorexia nervosa

“…With sufficient sample sizes, the imaging-genetics approach may improve how we classify eating disorders and prognosticate disorder risk and trajectory. Furthermore, coupling imaging and genetic research approaches may gain critical knowledge that improves the efficacy and safety for neuromodulation treatments for AN such as repetitive transcranial magnetic stimulation (Bartholdy et al, 2015) and deep brain stimulation (Lipsman and Lozano, 2014). Due to a lack of consensus on effective pharmacological treatment strategy (Treasure et al, 2015; Watson and Bulik, 2013), pharmacogenetic studies have yet to yield significant insights in changing treatments in the clinical setting (Adan and Vink, 2001; Gorwood, 2004; Monteleone and Maj, 2008).…”