Rationale and design of a double-blinded, randomized placebo-controlled trial of 40 Hz light neurostimulation therapy for depression (FELIX)

Abstract

Background

Major depressive disorder (MDD) is a debilitating condition that affects more than 300 million people worldwide. Current treatments are based on a trial-and-error approach, and reliable biomarkers are needed for more informed and personalized treatment solutions. One of the potential biomarkers, gamma-frequency (30–80 Hz) brainwaves, are hypothesized to originate from the excitatory-inhibitory interaction between the pyramidal cells and interneurons. The imbalance between this interaction is described as a crucial pathological mechanism in neuropsychiatric conditions, including MDD, and the modulation of this pathological interaction has been investigated as a potential target. Previous studies attempted to induce gamma activity in the brain using rhythmic light and sound stimuli (GENUS – Gamma Entrainment Using Sensory stimuli) that resulted in neuroprotective effects in Alzheimer’s disease (AD) patients and animal models. Here, we investigate the antidepressant, cognitive, and electrophysiological effects of the novel light therapy approach using 40 Hz masked flickering light for patients diagnosed with MDD.

Methods and design

Sixty patients with a current diagnosis of a major depressive episode will be enrolled in a randomized, double-blinded, placebo-controlled trial. The active treatment group will receive 40 Hz masked flickering light stimulation while the control group will receive continuous light matched in color temperature and brightness. Patients in both groups will get daily light treatment in their own homes and will attend four follow-up visits to assess the symptoms of depression, including depression severity measured by Hamilton Depression Rating Scale (HAM-D₁₇), cognitive function, quality of life and sleep, and electroencephalographic changes. The primary endpoint is the mean change from baseline to week 6 in depression severity (HAM-D₆ subscale) between the groups.

Keywords:

• Light stimulation
• major depressive disorder
• visual flicker
• 40 Hz stimulation
• gamma brainwaves
• cognition

Authors contributions

The primary investigator and sponsor of the trial is KM. KM and PMP conceived the presented idea, LS wrote and designed the clinical study and applied for funding opportunities, LSH found the EEG equipment, assisted in designing and reviewing the experimental protocols and randomization procedures, MSC provided support with the devices used for the study and investigator’s brochure, GMF programmed and calibrated devices used for the study and defined light characteristics, JMD and MPL were involved in clinical assessments and trial master file maintenance, KWM designed the neurocognitive battery, MN provided supervision to the Ph.D. student designing the clinical trial, LKHC provided statistical expertise. The study is registered on clinicatrials.gov, NCT05680220. Horizon 2020 project Astrotech funds the salary of the Ph.D. student and investigator of the trial. Study investigators KM and LS have applied and received further funding from the JaschaFonden.

Disclosure statement

The initiators of this project are KM and PMP. KM declares that he has no conflict of interest. PMP owns shares in the company OptoCeutics ApS. LS is an industrial Ph.D. student employed at OptoCeutics ApS, affiliated with DTU, and funded through Horizon2020 EU project Astrotech. MSC is CTO and owns shares in the company OptoCeutics ApS. MN is CEO and owns shares in the company OptoCeutics ApS. LSH is a full-time employee of OptoCeutics ApS and has stock options.

Data availability statement

After publication of the results, anonymized data can be made available from the principal investigator (K.M.) upon reasonable request.

Additional information

Funding

The Ph.D. student and investigator of the study (Laura Sakalauskaitė) is funded through the translational EU research project ASTROTECH (Marie Skłodowska-Curie Innovative Training Networks), hosted at the Technical University of Denmark, and employed full-time as an industrial Ph.D. at the medical device company OptoCeutics ApS. OptoCeutics ApS supply the devices and MENTALAB lends 8-channel Mentalab Explore wireless EEG equipment. Investigators have applied for and received additional funding from JaschaFonden [2023-0383] to sponsor study staff salaries and partly the devices used for the study.