BioClock—optimizing Bright Light Therapy for adults with depression: A study protocol for a multicenter randomized clinical trial on treatment strategies, response predictors, and chronobiological and neurobiological mechanisms

Background: Bright Light Therapy (BLT) is an effective treatment for various mood disorders, but challenges remain in optimizing its real-world administration, predicting individual responses, and understanding its mechanisms. Methods: This multicenter randomized controlled trial will enroll 231 patients with unipolar or bipolar depression, all currently experiencing a depressive episode. Participants will be randomized to one of three BLT interventions: (1) traditional home-based BLT, (2) BLT administered in the LightCafé—a novel setting promoting social interaction and lifestyle support, or (3) LightCafé BLT with personalized timing of both light and darkness by adding the use of blue light blocking glasses. The treatment duration will range from one to three weeks, based on preset definitions of participant’s response. The primary outcome is the change in depressive symptoms, assessed by a blinded rater. Secondary outcomes include subjective and objective sleep measures, circadian rhythm parameters from melatonin patterns and actigraphy, and functional outcomes. Change processes will be assessed using ecological momentary assessments of daily affect and energy levels, light exposure sensors, and via brain imaging. Discussion: This trial is the first to directly compare different BLT administration models, including a LightCafé setting. It aims to identify predictors of BLT response, investigate chronobiological and neurobiological mechanisms, and provide insights to optimize BLT for diverse patient populations. The results will inform clinical guidelines and enhance BLT's accessibility and effectiveness. Trial registration: Registered on July 14, 2023, at clinicaltrials.gov under number NCT05958940.