A Sequential Multiple Assignment Randomised Trial (SMART) of personalised treatment for Bulimia Nervosa and Binge Eating Disorder - TailorED

This is a multi-centre sequential multiple-assignment randomised trial (SMART) design. All participants will commence with four weeks of first-line treatment; namely, cognitive-behavioural therapy (CBT) guided self help (GSH). The InsideOut Institute for Eating Disorders at the University of Sydney has developed an online CBT intervention called Binge Eating eTherapy (BEeT). Participants will commence with four weeks of BEeT(GSH) which will include weekly online eTherapy modules delivered alongside 30-minute weekly one-to-one telehealth sessions with a guide who is a registered or provisionally registered mental health professional. Eligible participants who have completed baseline assessments for the Holistic Understanding Study (Trial Id: ACTRN12625000731493) will commence participation in the TailorED trial within 1 week of completing HU baseline assessments. The first four weeks introduce participants to BEeT(GSH). Each weekly module consists of approximately 60 minutes of self-directed online eTherapy modules followed by a 30-minute weekly one-to-one telehealth sessions with a guide. Orientation covers program structure, treatment goals, pre-treatment review, safety planning, and weekly weighing. Core modules teach CBT principles, goal setting, the binge eating cycle, and self-monitoring. Subsequent sessions reinforce these foundations, focusing on personalised formulation, motivation to change, structured eating, and planning ahead. Participants learn to implement regular eating, identify triggers, use pleasant and distracting activities, and address compensatory behaviours. Week four consolidates coping strategies and includes a wrap-up call to determine next treatment steps. After 4 weeks of BEeT(GSH), response to treatment will be assessed and participants will be categorised according to well established criteria as either rapid responders (RR) or non-rapid responders (NRR) to treatment (Russell et al., 2023, Thompson-Brenner et al., 2025). RR are defined as those reporting at least a 70% reduction in binge eating episodes. NRR are defined as those reporting less than a 70% reduction in binge eating episodes. All randomly allocated treatments continue immediately after the 4-weeks of first line treatment. All RR after four weeks of first-line treatment will be randomly allocated to continue with a further six weeks of: a) BEeT(GSH) (online eTherapy modules approximately 60 minutes in length delivered alongside 30-minute weekly one-to-one telehealth sessions with a guide who is a registered or provisionally registered mental health professional), or b) weekly BEeT online eTherapy modules with one-to-one ‘light contact’ from a registered or provisionally registered mental health professional. ‘Light contact’ means 5-10 minutes of non-clinical contact per week between guide and participant via email, text message or phone to ensure participants have what they need to complete the program week. All NRR after four weeks of first-line treatment will be randomly allocated to continue with 16 weeks of a) BEeT(GSH) (online eTherapy modules approximately 60 minutes in length delivered alongside 30-minute weekly one-to-one telehealth sessions with a guide who is a registered or provisionally registered mental health professional totalling 24 hours of intervention over 16 weeks), b) a personalised package of psychotherapy 90 minutes per week (totalling 24 hours of intervention over 16 weeks), or c) a learning enhanced transcranial magnetic stimulation (TMS) treatment package (totalling 24 hours of intervention over 16 weeks). BEeT Therapy: RR participants assigned to either the BEeT(GSH) or BEeT(LC) arms will continue on from the first-line treatment administered in the initial 4 weeks of treatment for an additional 6 weeks (10 weeks of BEeT total). The online content will be consistent between the two randomisation arms, with the only variant being the type and amount of guided support provided by the clinician. Sessions 5–10 extend CBT skills and deepen behavioural and cognitive strategies. Participants continue weekly check-ins and weighing, with ongoing review of self-monitoring accuracy. Session 5 introduces problem-solving and explores the role of emotions in binge eating, teaching skills for identifying and managing emotional triggers. Session 6 focuses on emotion regulation, including noticing, validating, and expressing feelings, and introduces monitoring thoughts and unhelpful thinking patterns. Session 7 builds on this by teaching thought-challenging techniques and practicing them using the Toolbox. Session 8 addresses feared foods and rigid food rules, introducing exposure strategies and creating hierarchies for challenging these fears. Session 9 shifts to body image concerns, avoidance and checking behaviours, and introduces urge surfing as a coping skill. Session 10 consolidates learning with relapse prevention planning, body acceptance, self-compassion, and identifying values and strengths, while reflecting on progress and preparing for long-term recovery. NRR participants assigned to the BEeT(GSH) will continue on from the first-line treatment administered in the initial 4 weeks of treatment for an additional 16 weeks (20 weeks of BEeT(GSH) total). This content is consistent with that provided to the RR BEeT arms, with the same CBT-based modules but with greater depth, more gradual progression, and repeated practice. Additional sessions allow for troubleshooting barriers, reinforcing skills like emotion regulation and thought challenging, and expanding exposure work for food and body image concerns. The extended format also includes more time for reflection, values-based work, and relapse prevention planning to strengthen long-term recovery. This extended version of the online BEeT content has been specifically developed for this study. Personalised Psychotherapy: Participants randomised to personalised package of psychotherapy (PEP) will receive a highly personalised measurement-based care package delivered one-to-one by a psychologist via telehealth or face-to-face. Personalised psychotherapy will take a fully modularised approach, whereby components of evidence-based therapies will be delivered according to individual characteristics and collaboratively identified treatment targets. Modules are drawn from best-practice examples of evidence-based therapies in and beyond eating disorders and focus on a range of concepts relevant to Bulimia Nervosa (BN) and Binge Eating Disorder (BED). Eight modules are available, targeting: 1) lifestyle routines and self-care, 2) decision making and planning, 3) body image and weight stigma, 4) relationships and connection, 5) emotion regulation, 6) impulse control and cravings, 7) self-worth and self-compassion, and 8) motivation and commitment to change. Each module is designed to take approximately 360-minutes, which will be administered in four 90-minute sessions over four weeks. PEP will commence with: development of an expanded, personalised shared formulation incorporating baseline data (this will be a live document throughout the intervention and informed by ongoing monitoring data (including Ecological Momentary Assessment [EMA], treatment response data, clinician and client perspective, and comprehensive problem-solving training, and comprehensive and repeated chain analysis. This information alongside collection of EMA items assessing symptom presence will be used during a shared decision-making meeting to decide on treatment targets and the assignment of modules to address them. At the end of each module, EMA items will be collected again to determine if the current assigned modules should continue or other modules be assigned, and the formulation (based on ongoing data collection, problem solving, and chain analyses, and progress through therapy) will be updated and also taken into the shared decision making meeting for module assignment. PEP will end with 2 weeks of relapse prevention and discharge planning. Treatment will be delivered online and will be supported by written and/or online materials. Transcranial Magnetic Stimulation Treatment Package: The NRRs randomly allocated to the personalised Transcranial Magnetic Stimulation (TMS) package will receive a highly tailored, measurement-based care package comprised of motivational interviewing, cognitive exercises, and TMS modules. The TMS package modules are drawn from best-practice examples of evidence-based interventions in and beyond eating disorders and may focus a range of concepts relevant to BN and BED including difficulties with cognitive control and reward processing (Colton et al., 2023). The motivational interviewing will be delivered weekly, beginning in the first week post randomisation (Week 5). Participants will undergo three sessions over a three-week period, to a total of 105 minutes. The aim of the motivational interviewing is to increase participants' readiness for TMS. The motivational interview will be administered by provisional or registered psychologists via videoconferencing platform (Zoom). During this clinician facing time, participants will also perform their weekly weigh-ins. From the second week of the TMS package (Week 6), a pre-existing digital neurorehabilitation platform, NeuronUp (https://neuronup.us/), will be used to conduct personalised cognitive exercises. Participants will complete 30 minutes of training five times per week over a two-week period, to a total of 300 minutes. Training will be completed at home in the participants' time using the NeuronUp2Go feature, a tailored account for participants which can be accessed on their computer. The mode of intervention used in NeuronUp will be primarily games. These activities are organised in different levels of difficulty so that the participant will move forward or backward automatically depending on their successes/mistakes – in this way the program delivered is personalised to the person’s capacity. Games can also be customised to suit each participant's needs (e.g., timing, number of exercises, number of stimuli or targets, maximum errors allowed). Both the motivational and NeuronUp content will be followed by five consecutive days of accelerated theta-burst stimulation (iTBS) delivered over the left dorsolateral prefrontal cortex, start in Week 8. This will occur at Royal Prince Alfred Hospital, Camperdown NSW and Monash University, School of Psychological Sciences, Clayton VIC. Participants recruited through the West Wodonga VIC site will be assisted to travel to the Clayton VIC site to complete iTBS intervention. The iTBS approach is modelled on the FDA-approved (K220177) Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol (Cole et al., 2020). We will mimic the stimulation parameters of this widely used protocol for the treatment of depression (up to 1,800 pulses per TMS dose at up to 110% of the resting motor threshold). Participants will undergo three iTBS doses each session (day), with 50 minutes between each dose. Each TMS dose will last approximately 20 minutes, including 5 minutes for preparation, 3 minutes for adaptation, and ~10 minutes of stimulation. The burst pattern consists of three pulses at 50 Hz, with 10 bursts delivered in two second trains (5 Hz) followed by an eight-second inter-train interval, for a total of 60 cycles. In the first TMS dose on Day one, the Resting Motor Threshold procedure will be conducted (~10 minutes). After each dose, a non-invasive brain stimulation poststimulation Interview (~10 minutes) will be administered. Therefore, participants will need to commit approximately 4.5-5 hours per day for 5 days of TMS treatment. Following TMS (Weeks 9-20), participants will complete a further 12 weeks of cognitive training on NeuronUp, via the NeuronUp2Go feature, focused on generalisation of cognitive learnings into daily life activities. During these weeks, participants will also meet with a clinician for a brief 10-20 minute weekly check-in via Zoom to complete weigh-ins and discuss the weekly content and progress. For the final check-in at Week 20, discharge planning and relapse prevention will be covered. Fidelity Checks: Clinicians will complete session logs and fidelity checklists to document treatment delivery and adherence to the interventions. Between 10% and 50% of therapy sessions will be audio-recorded to assess treatment fidelity and support clinical supervision. Recordings will be reviewed using a standardised fidelity checklist to ensure adherence to the treatment model.