title: 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: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ISRCTN14329415 . Date of registration: 23 July 2015.
authors.affiliation: Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. savani.bartholdy@kcl.ac.uk.
authors.forename: Savani
authors.initials: S
authors.lastname: Bartholdy
authors.affiliation: Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. jessica.mcclelland@kcl.ac.uk.
authors.forename: Jessica
authors.initials: J
authors.lastname: McClelland
authors.affiliation: Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. maria.kekic@kcl.ac.uk.
authors.forename: Maria
authors.initials: M
authors.lastname: Kekic
authors.affiliation: Centre for Neuroimaging Sciences, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. o.o'daly@kcl.ac.uk.
authors.forename: Owen G
authors.initials: OG
authors.lastname: O'Daly
authors.affiliation: Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. iain.campbell@kcl.ac.uk.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Campbell
authors.affiliation: Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. jessica.werthmann@kcl.ac.uk.
authors.forename: Jessica
authors.initials: J
authors.lastname: Werthmann
authors.affiliation: Centre for Neuroimaging Sciences, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. samantha.rennalls@kcl.ac.uk.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Rennalls
authors.affiliation: Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. katya.rubia@kcl.ac.uk.
authors.forename: Katya
authors.initials: K
authors.lastname: Rubia
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. anthony.david@kcl.ac.uk.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: David
authors.affiliation: South London and Maudsley NHS Foundation Trust, London, UK. danielle.glennon@slam.nhs.uk.
authors.forename: Danielle
authors.initials: D
authors.lastname: Glennon
authors.affiliation: South London and Maudsley NHS Foundation Trust, London, UK. nikola.kern@slam.nhs.uk.
authors.forename: Nikola
authors.initials: N
authors.lastname: Kern
authors.affiliation: Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. ulrike.schmidt@kcl.ac.uk.|South London and Maudsley NHS Foundation Trust, London, UK. ulrike.schmidt@kcl.ac.uk.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schmidt
mesh_terms: D000856:Anorexia Nervosa / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D015992:Body Mass Index; D001921:Brain / Q000503:physiopathology*; D002985:Clinical Protocols; D004311:Double-Blind Method; D005240:Feasibility Studies; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D008131:London; D008297:Male; D059906:Neuroimaging / Q000379:methods; D017060:Patient Satisfaction; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life; D012107:Research Design; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D065908:Transcranial Direct Current Stimulation / Q000009:adverse effects; D016896:Treatment Outcome