BioClock: Bright Light Therapy for Depressive Disorders

Official title

BioClock: Optimization, Working Mechanisms and Response Predictors of Bright Light Therapy for Depressive Disorders - a Multicentre Randomized Controlled Trial

Overview

Bright Light Therapy (BLT) is a proven treatment for depression in seasonal and non-seasonal depressive disorders, as well as bipolar disorder. To make BLT more effective and practical in clinical settings and tailor it to individual needs, it is necessary to optimize the treatment approach, understand how the treatment works, and identify patient characteristics that predict response. This clinical trial has three main goals: * Optimize the administration of BLT for patients with depressive episodes. * Gain a deeper understanding of the treatment mechanisms. * Determine which patients benefit the most from the treatment. The specific objectives are as follows: * Investigate whether additional treatments and interventions related to lifestyle and the biological clock can enhance the effects of BLT. * Examine how BLT influences the body's internal clock and sleep quality, and how these factors contribute to the outcomes. * Identify patient characteristics and behaviours that can predict treatment outcomes. * Develop a brain model to better understand the impact of BLT on the brain. In this study, patients will receive BLT with a light intensity of 10,000 lux for 30 minutes each morning over 5 consecutive days. The treatment duration will range from one to three weeks, depending on the improvement of depressive symptoms. Participants will be randomly assigned to one of three groups: * Home - Patients will receive BLT at home, following the standard guidelines for light therapy in the Netherlands. * LightCafé, fixed time: Patients will receive BLT in a café-like setting called the LightCafé, where the focus is not only on symptom improvement but also lifestyle enhancements and fostering social connections. The treatment time will be the same every day. * LightCafé, varying time: Patients will also receive BLT at the LightCafé, with treatment timing varying each day. Additionally, this group will wear glasses in the evening that filter blue light. The study includes a baseline phase of up to two weeks, a treatment phase of up to three weeks, and a three-month follow-up phase. Patients will wear a motion watch to assess sleep-wake behaviour and physical activity during the day. Additionally, they will wear a broach that measures their personal light exposure throughout the day. Eight one-minute questionnaires per day will be sent to the participants' smartphones to assess vitality, sleep, and mood during the treatment. Predictors of treatment response, such as clinical characteristics, sleep measures, circadian parameters, and light-related behaviours, will be evaluated at baseline. In a small group of patients, salivary melatonin curves will be assessed before and after treatment. MRI scans will provide insights into functional and structural brain changes following light therapy treatment.

Interventions

• Procedure Bright Light Therapy
  In this study, Bright Light Therapy (BLT) will be administered according to Dutch depression guidelines, using Innolux LED light lamp (3800K, 10,000 lux). BLT will be given for one work week (Mon-Fri), 7:30-10:30 AM, 30 mins/session. Patients can have breakfast, read, or use devices. Treatment effectiveness will be evaluated using Self-Rated Quick Inventory of Depressive Symptoms (QIDS-SR). If remission is achieved (QIDS-SR \< 6), no additional treatment is given. If response is insufficient (QI
• Device Blue Light Blocking Glasses
  Plastic, orange-coloured glasses that primarily block blue light. To be worn in the evening.

Primary outcome measures

• Clinical Improvement [Time frame: 2-5 weeks]

Secondary outcome measures (12)

• Subjective change in depressive symptom severity [Time frame: from baseline until follow-up, approximately 4 months]
• Remission rates, self assessed and clinician rated [Time frame: 2-5 weeks for clinician rated. Up until 4 months after start treatment for self-assessed]
• Response Rates, self assessed and clinician rated [Time frame: 2-5 weeks for clinician rated, Up until 4 months after start treatment for self-assessed]
• Time to remission [Time frame: one, two or three weeks]
• Circadian phase [Time frame: 2-5 weeks]
• Circadian amplitude [Time frame: 2-5 weeks]
• Circadian Periodicity [Time frame: 2-5 weeks]
• Inter-daily stability [Time frame: 2-5 weeks]
• Intra-daily variability [Time frame: 2-5 weeks]
• Chronotype [Time frame: 1-3 months]
• Sleep-Wake Pattern [Time frame: 2-5 weeks]
• Sleep Quality [Time frame: 2-5 weeks for actigraphy, up until 4 months after the start of treatment for subjective sleep quality]

Eligibility criteria

Inclusion criteria

• Age between 18 and 65.
• Diagnosis of unipolar or bipolar depression (seasonal or non-seasonal) as assessed with the Mini-International Neuropsychiatric Interview (M.I.N.I.)
• A current depressive episode (a score of 6 or higher on the Quick Inventory of depressive symptomatology Self Report (QIDS-SR)
• Sufficient knowledge of Dutch or English language to fill in questionnaires
• Provided Informed consent

Exclusion criteria

• A current (hypo)manic or mixed episode (as assessed with the M.I.N.I.)
• Current psychotic episode (as assessed with the M.I.N.I.)
• Prominent active suicidality (score 10 or higher on the M.I.N.I. module)
• Antidepressant therapy (medication, psychotherapy or BLT, or other forms of specific treatments for depression) that started less than 2 months prior to study entry
• participants with bipolar disorder should be in mood-stabilizing treatment for at least 1 month in a recommended dosage,
• Use of melatonin or agomelatine in the last month
• Current use of antibiotics
• Current use of light sensitivity increasing medication
• Travelled across more than 1 time zone during past month or during the treatment
• Travelled to sunny holiday locations/winter sports during past month
• pre-existing eye and skin disorders (retinitis pigmentosa, porphyria, chronic actinic dermatitis and sun-induced urticaria)
• Systemic disorders with potential retinal involvement (rheumatoid arthritis and systemic lupus erythematosus)
• Suffering from colour blindness (assessed by Ishihara colour plates)
• Participated in night shift work in the last three months
• (Retinal) blindness, severe cataract and glaucoma
• Light-induced migraine or epilepsy
• Pregnancy, or parents with a child younger than 18 months old

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Netherlands · 2 centers

• GGzE - Mental Health Institute of Eindhoven and the Kempen — Eindhoven
• Leids Universitair Behandel- en Expertise Centrum — Leiden

Publications

• Visser E, Rus-Oswald OG, van der Does AJW, Gordijn MCM, Marcelis MC, de Kort YAW, Oomen PP, Schlangen LJM, Seetsen T, Simons CJP, Antypa N. 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. Trials. 2025 Oct 14;26(1):411. PMID 41088238

Identifiers

NCT: NCT05958940 · NL83497.058.23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗