HALO-TRIAL: high, Medium And LOw Intensity Psychotherapy for Binge Eating Disorder

The HALO trial is a investigator‐initiated, four‐arm, partially blinded, randomizedcontrolled superiority trial evaluating the effectiveness of three formats andintensities of Cognitive Behavioral Therapy‐Enhanced (CBT‐E) compared with manualizedtreatment as usual (TAU) for adults with Binge Eating Disorder (BED).BED is associated with substantial psychiatric and physical morbidity, and despitepsychotherapy being the recommended first‐line treatment, there is limited high‐qualityevidence directly comparing different CBT‐E delivery formats compared with an activecontrol intervention. The trial aims to determine whether individual CBT‐E providessuperior clinical outcomes compared with group CBT‐E, CBT‐E guided self‐help, andmanualized TAU.A total of 256 participants with a primary diagnosis of BED will be recruited throughDanish Mental Health Services and public advertisement. Following informed consent andbaseline diagnostic assessments, eligible participants will be randomized in a 1:1:1:1ratio to one of four treatment arms: (1) individual CBT‐E, (2) group CBT‐E, (3)therapist‐guided CBT‐E self‐help, or (4) manualized group‐based systemic narrativetherapy delivered as treatment as usual. All interventions are delivered over a 21‐weektreatment period.Diagnostic assessments include the Eating Disorder Examination interview to confirm thediagnosis of BED and the Mini International Neuropsychiatric Interview to assesspsychiatric comorbidity and study eligibility. The primary outcome is change in bingeeating frequency measured using the Eating Disorder Examination Questionnaire. Secondaryoutcomes include remission from BED assessed by the Eating Disorder Examinationinterview, overall eating disorder psychopathology (Eating Disorder ExaminationQuestionnaire), psychological well‐being (World Health Organization‐Five Well‐BeingIndex), work and social functioning (Work and Social Adjustment Scale), anxiety symptoms(State‐Trait Anxiety Inventory), and depressive symptoms (Beck Depression Inventory‐II).In addition, a broad range of exploratory psychological, clinical, and psychosocialmeasures will be collected to investigate potential mechanisms of treatment response,predictors of outcome, and moderators and mediators of treatment effects (list ofexploratory outcomes is available upon request). These exploratory measures are used onlyfor hypothesis‐generating and are not part of the primary efficacy analyses.Post‐treatment diagnostic interviews are conducted by blinded outcome assessors. Due tothe nature of the psychotherapeutic interventions, participants and therapists cannot beblinded to treatment allocation. Outcome assessors, statisticians, investigatorsresponsible for data analysis, and the trial leadership remain blinded until completionof the primary analyses.To ensure intervention fidelity, therapists receive standardized training and ongoingmethod‐specific supervision throughout the trial. Treatment sessions are video‐recorded,and a random sample (10%) will be independently assessed for adherence to the treatmentmanuals. Assessors receive regular supervision, and inter‐rater reliability is monitoredthroughout the study.Participant safety is monitored throughout the trial. Serious adverse events andclinically significant deterioration are documented according to predefined procedures.Participants identified as having severe depression or elevated suicide risk are managedaccording to standardized clinical safety procedures. All participants provide writteninformed consent prior to study participation.Study data are collected and managed using the secure electronic data capture systemREDCap, which complies with applicable data protection regulations. Data quality isensured through standardized assessment procedures, predefined data collection protocols,electronic range and consistency checks, and regular monitoring of study procedures.The primary analysis will follow the intention‐to‐treat principle, including allrandomized participants according to their allocated treatment group regardless oftreatment adherence. Continuous outcomes will be analyzed using mixed‐effects regressionmodels for repeated measures, while dichotomous outcomes will be analyzed using logisticregression models. Secondary outcome analyses will account for multiple testing whereappropriate. Missing outcome data will be handled using likelihood‐based mixed modelsunder the missing‐at‐random assumption, with multiple imputation used for secondaryanalyses and missing baseline covariates. If substantial evidence suggests that data areMissing Not At Random, sensitivity analyses will be undertaken. A supplementaryper‐protocol analysis may be conducted if dropout exceeds assumptions used in the samplesize calculation.The planned sample size of 256 participants (64 per treatment arm) was based on a prioripower calculations assuming a small‐to‐moderate treatment effect (Cohen's f = 0.20), atwo‐sided significance level of 0.05, and approximately 85% statistical power in theprimary mixed‐model repeated measures analysis, while accounting for an anticipatedattrition rate of up to 30%. This sample size is expected to provide adequate power todetect clinically meaningful differences between treatment groups. With a planned samplesize of 256 participants, the HALO trial is expected to be the largest randomizedclinical trial of psychotherapy for BED conducted to date and will provide robustevidence regarding the comparative effectiveness of different CBT‐E treatment formats andmanualized treatment as usual.