Study purpose: The main aim is to assess and compare the effect(s) of each of the four doses of the Near-infrared Transcranial Laser Therapy (NIR-TLT) on the symptomatology of depression: antidepressant effect, in subjects with major depressive disorder (MDD). Study design: This protocol is a multicentered, randomized, simulated, and double-blind clinical study. This work will randomize 112 subjects into 4 equal groups: bilateral continuous wave (BCW), bilateral pulsed wave (BPW 1-2) y SHAM. All subjects, investigators (except the study statistician), and outcomes assessors will be blind to group assignment. The device operator will be aware of group assignments. All subjects will receive 3 NIR-TLT treatments per week for 6 weeks. A follow-up evaluation will be performed 2 weeks after the end of the study. The treatment will follow these specifications: wavelength 830 nm; average irradiance 54,8 mW / cm2; average fluence of 65,8 J / cm2 (consistently with parameters used in the ELATED-2 study at MGH with the device Omnilux New U), being the total Fluency delivered: 3.6 kJ (bilateral) o 1.8 kJ (unilateral), either on the subject's forehead, at or near electroencephalography sites (EEG) F3 and F4. All NIR-TLT sessions will last 20 minutes, regardless of group assignment. Study population: Patients eligible for study participation will be diagnosed with major depressive disorder (MDD) by DSM criteria. Subjects will be between 18-75 years of age (have not had 76st birthday) on the date of screening. Duration of participation: Subjects will be followed in the study for 8 weeks (a 6-week treatment period, plus 2 weeks of follow-up). The total duration of the study will be 24 months. Assessment criteria: The primary efficacy criteria is the improvement in depressive symptoms from each of the four doses of NIR-TLT. Assessed using HAMD-17, at 3 time points (visit 1, visit 9 and visit 18).
The Near-infrared transcranial laser therapy (NIR-TLT) is a non-ionizing electromagnetic wave. The NIR-TLT is invisible, penetrates the skin and skull into brain tissue and is non-invasive. The benefits of NIR-TLT are wavelength specific. A mitochondrial enzyme, the Cytochrome c oxidase, is the primary chromophore for the NIR-TLT with a wavelength of around 830 nm. When this enzyme is activated, it leads to increased adenosine triphosphate (ATP) production and this event is related to the promotion of cellular plasticity and cytoprotection. These are critical cellular processes for recovery of the depressive patients. Therefore, this study will contribute to answer the question of whether NIR-TLT has an antidepressant effect and whether it is acceptable in minority population.