Description

The HALO trial is a investigator-initiated, four-arm, partially blinded, randomized controlled superiority trial evaluating the effectiveness of three formats and intensities of Cognitive Behavioral Therapy-Enhanced (CBT-E) compared with manualized treatment as usual (TAU) for adults with Binge Eating Disorder (BED).

BED is associated with substantial psychiatric and physical morbidity, and despite psychotherapy being the recommended first-line treatment, there is limited high-quality evidence directly comparing different CBT-E delivery formats compared with an active control intervention. The trial aims to determine whether individual CBT-E provides superior clinical outcomes compared with group CBT-E, CBT-E guided self-help, and manualized TAU.

A total of 256 participants with a primary diagnosis of BED will be recruited through Danish Mental Health Services and public advertisement. Following informed consent and baseline diagnostic assessments, eligible participants will be randomized in a 1:1:1:1 ratio 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 narrative therapy delivered as treatment as usual. All interventions are delivered over a 21-week treatment period.

Diagnostic assessments include the Eating Disorder Examination interview to confirm the diagnosis of BED and the Mini International Neuropsychiatric Interview to assess psychiatric comorbidity and study eligibility. The primary outcome is change in binge eating frequency measured using the Eating Disorder Examination Questionnaire. Secondary outcomes include remission from BED assessed by the Eating Disorder Examination interview, overall eating disorder psychopathology (Eating Disorder Examination Questionnaire), psychological well-being (World Health Organization-Five Well-Being Index), 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 psychosocial measures will be collected to investigate potential mechanisms of treatment response, predictors of outcome, and moderators and mediators of treatment effects (list of exploratory outcomes is available upon request). These exploratory measures are used only for hypothesis-generating and are not part of the primary efficacy analyses. Post-treatment diagnostic interviews are conducted by blinded outcome assessors. Due to the nature of the psychotherapeutic interventions, participants and therapists cannot be blinded to treatment allocation. Outcome assessors, statisticians, investigators responsible for data analysis, and the trial leadership remain blinded until completion of the primary analyses.

To ensure intervention fidelity, therapists receive standardized training and ongoing method-specific supervision throughout the trial. Treatment sessions are video-recorded, and a random sample (10%) will be independently assessed for adherence to the treatment manuals. Assessors receive regular supervision, and inter-rater reliability is monitored throughout the study.

Participant safety is monitored throughout the trial. Serious adverse events and clinically significant deterioration are documented according to predefined procedures. Participants identified as having severe depression or elevated suicide risk are managed according to standardized clinical safety procedures. All participants provide written informed consent prior to study participation.

Study data are collected and managed using the secure electronic data capture system REDCap, which complies with applicable data protection regulations. Data quality is ensured 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 all randomized participants according to their allocated treatment group regardless of treatment adherence. Continuous outcomes will be analyzed using mixed-effects regression models for repeated measures, while dichotomous outcomes will be analyzed using logistic regression models. Secondary outcome analyses will account for multiple testing where appropriate. Missing outcome data will be handled using likelihood-based mixed models under the missing-at-random assumption, with multiple imputation used for secondary analyses and missing baseline covariates. If substantial evidence suggests that data are Missing Not At Random, sensitivity analyses will be undertaken. A supplementary per-protocol analysis may be conducted if dropout exceeds assumptions used in the sample size calculation.

The planned sample size of 256 participants (64 per treatment arm) was based on a priori power calculations assuming a small-to-moderate treatment effect (Cohen's f = 0.20), a two-sided significance level of 0.05, and approximately 85% statistical power in the primary mixed-model repeated measures analysis, while accounting for an anticipated attrition rate of up to 30%. This sample size is expected to provide adequate power to detect clinically meaningful differences between treatment groups. With a planned sample size of 256 participants, the HALO trial is expected to be the largest randomized clinical trial of psychotherapy for BED conducted to date and will provide robust evidence regarding the comparative effectiveness of different CBT-E treatment formats and manualized treatment as usual.