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Connectivity guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistant moderate to severe depression: study protocol for a randomised double-blind controlled trial (BRIGhTMIND)
  1. Richard Morriss1,
  2. Lucy Webster2,
  3. Mohamed Abdelghani3,
  4. Dorothee P Auer4,5,
  5. Shaun Barber6,
  6. Peter Bates7,
  7. Andrew Blamire8,
  8. Paul M Briley9,
  9. Cassandra Brookes10,
  10. Sarina Iwabuchi9,
  11. Marilyn James11,
  12. Catherine Kaylor-Hughes9,
  13. Sudheer Lankappa2,
  14. Peter Liddle9,
  15. Hamish McAllister-Williams8,
  16. Alex O'Neill-Kerr12,
  17. Stefan Pszczolkowski Parraguez13,
  18. Ana Suazo Di Paola10,
  19. Louise Thomson1,
  20. Yvette Walters10
  21. BRIGhTMIND study team
    1. 1Psychiatry, University of Nottingham, Nottingham, UK
    2. 2Nottinghamshire Healthcare NHS Foundation Trust, Nottingham, Nottingham, UK
    3. 3Camden and Islington NHS Foundation Trust, London, London, UK
    4. 4Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, Nottinghamshire, UK
    5. 5Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
    6. 6University of Leicester, Leicester, Leicestershire, UK
    7. 7Nottingham, UK
    8. 8University of Newcastle upon Tyne, Newcastle upon Tyne, Tyne and Wear, UK
    9. 9University of Nottingham, Nottingham, Nottinghamshire, UK
    10. 10Leicester Clinical Trials Unit, University of Leicester, Leicester, UK
    11. 11School of Medicine, University of Nottingham, nottingham, UK
    12. 12Northamptonshire Healthcare NHS Foundation Trust, Kettering, Northamptonshire, UK
    13. 13Precision Imaging Beacon, University of Nottingham, Nottingham, UK
    1. Correspondence to Professor Richard Morriss; richard.morriss{at}nottingham.ac.uk

    Abstract

    Introduction The BRIGhTMIND study aims to determine the clinical effectiveness, cost-effectiveness and mechanism of action of connectivity guided intermittent theta burst stimulation (cgiTBS) versus standard repetitive transcranial magnetic stimulation (rTMS) in adults with moderate to severe treatment resistant depression.

    Methods and analysis The study is a randomised double-blind controlled trial with 1:1 allocation to either 20 sessions of (1) cgiTBS or (2) neuronavigated rTMS not using connectivity guidance. A total of 368 eligible participants with a diagnosis of current unipolar major depressive disorder that is both treatment resistant (defined as scoring 2 or more on the Massachusetts General Hospital Staging Score) and moderate to severe (scoring >16 on the 17-item Hamilton Depression Rating Scale (HDRS-17)), will be recruited from primary and secondary care settings at four treatment centres in the UK. The primary outcome is depression response at 16 weeks (50% or greater reduction in HDRS-17 score from baseline). Secondary outcomes include assessments of self-rated depression, anxiety, psychosocial functioning, cognition and quality of life at 8, 16 and 26 weeks postrandomisation. Cost-effectiveness, patient acceptability, safety, mechanism of action and predictors of response will also be examined.

    Ethics and dissemination Ethical approval was granted by East Midlands Leicester Central Research Ethics Committee (ref: 18/EM/0232) on 30 August 2018. The results of the study will be published in relevant peer-reviewed journals, and then through professional and public conferences and media. Further publications will explore patient experience, moderators and mediators of outcome and mechanism of action.

    Trial registration number ISRCTN19674644

    • depression & mood disorders
    • magnetic resonance imaging
    • health economics
    • adult psychiatry
    • clinical trials
    https://creativecommons.org/licenses/by/4.0/

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    Footnotes

    • Collaborators BRIGhTMIND study team: Lorraine Bastick, Rosie Carr, Alison Cartlidge, Harry Clark, William Cottam, Robert De Vai, Linda Davison, John Gledhill, Adele Gregory, Christopher Griffiths, Andrew Hamilton, Delilah Harding, Kelly Heath, Rachel Hobson, Gbeminiyi Ireoluwa, Najat Khalifa, Kate Johnstone, Charlotte Kirkland, Mark Liddle, Jessica Lynch, Neil Nixon, Jehill Parikh, Isabel Reid, Noemi Reiner, Sandra Simpson, Beverley Smith, Tina Sore, Joseph Stone, Carly Taylorson, Rebecca Toney, Claire Turner, Sarah Wilkinson, Andy Willis, Tom Willis.

    • Contributors All authors approved the final manuscript. RM is the chief investigator and guarantor of the project. He designed the study, obtained funding and wrote the final draft of the protocol. LW wrote operational guidelines for the project, qualitative analysis protocols and the first draft on this manuscript. MA is the principal investigator for the London site, obtained funding, and designed the TMS schedules. DPA is the neuroimaging lead, led some of the underpinning work designed the neuroimaging and obtained grant funding. SB carried out power calculations for the study and designed the statistical analysis. PB has led the patient and public involvement aspects of the project and their contributions to the operation of the project. AB designed the neuroimaging and obtained grant funding. PMB designed some of the neuroimaging protocol and is analysing the imaging data. CB designed the statistical analysis and obtained funding for the study. SI led some of the underpinning work, designed the neuroimaging and TMS parts of the protocol and obtained funding. MJ designed the health economic analysis, the health economic data collection forms and will be responsible for the health economic management of the trial and oversee all the health economic analysis. CK-H wrote protocols for TMS in the study and carried out some of the neuroimaging analysis. AO-K is the principal investigator for the Northampton site, obtained funding, and designed the TMS schedules. SL, the principal investigator for the Nottingham site, carried out some of the underpinning work, obtained funding, and designed the TMS schedules. PL carried out some of the underpinning work and designed some of the neuroimaging and TMS work, and obtained funding. HM-W is the principal investigator for the Newcastle site, designed the cognitive assessment and assessment of treatment resistance and obtained funding. SPP designed and carried out the computer programming for TMS site location, helped design the Neuronavigation and TMS protocols, and is carrying out neuroimaging analysis. ASDP designed the Statistical Analysis Plan and is carrying out the statistical analysis. LT is the qualitative research lead, designed the qualitative parts of the project and obtained funding. YW is the trial manager of the study and has led the writing of study operating procedures, ethics and governance protocols for the study.

    • Funding This project (project reference 16/44/22) is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership. Equipment for the study was provided by Magstim Company. SponsorResearch and Evidence Team, Nottinghamshire Healthcare NHS Foundation Trust. The views expressed in this publication are those of the author(s) and not necessarily those of the MRC, NIHR, Magstim Company or the Department of Health and Social Care.

    • Disclaimer The views expressed in this publication are those of the author(s) and not necessarily those of the MRC, NIHR, Magstim Company or the Department of Health and Social Care.

    • Competing interests AO-K has received fees for consultancy with Magstim.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.