Near-infrared Radiation-transcranial Photobiomodulation for Major Depressive Disorder
Condition: Major Depressive Disorder; Oxidative Stress
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional

Summary: 
      This study was designed to be a 3 year, 3 phases project, and will explore the therapeutic
      effects from near-infrared transcranial photobiomodulation (NIR tPBM) in major depressive
      disordered human subjects, and it's biological mechanisms in cellular and animal model.
      However, due to shortage of funding under the pandemics, the project is now modified to start
      from its clinical part first, and will continue to its basic parts later when funding
      resources in place.
    

Detailed description: 
      Major depressive disorder (MDD) is a leading cause of the overall global burden of disease in
      modern society, and has been estimated to move into the first place by 2030. Current
      antidepressants and psychotherapy had proved their efficacy, but are limited by the adverse
      effects and shortage of capable therapists worldwide. Accumulating evidence showed that
      hypometabolism of global and specific brain regions, inflammation, oxidative stress,
      suppression of neurogenesis and disturbed circadian rhythm all contribute to the
      pathophysiology of MDD.

      Dr. Paolo Cassano, MD, PhD and his team from the Massachusetts General Hospital (MGH) of
      Harvard University recently demonstrated in both animal and human subjects that near-infrared
      radiation-transcranial photobiomodulation (NIR-tPBM) is a well-tolerated and effective
      treatment modality for MDD, and hypothesized NIR-tPBM may activate brain metabolism, be
      anti-inflammatory, reduce oxidative stress and promote neurogenesis. So far, the clinical
      studies are either open-labeled or only of small scale (n=21), and the real antidepressant
      mechanism of NIR-tPBM has not yet been fully understood. Adequately powered, well designed,
      double-blind randomized-control trials of larger scale is in pressing need.

      In this 3-year study, we will collaborate with the team from Harvard University and MGH, to
      comprehensively evaluate from cellular mechanism, animal model, to clinical trials in human,
      the underlying mechanism of NIR-tPBM and the clinical strategy of NIR-tPBM. In the cellular
      study, we will culture and treat the human neuron-like cell lines with continuous NIR-PBM of
      different dosimetry and different duration, and compare the differences in cellular circadian
      rhythm, energy metabolism, and inflammation markers as well as the underlying gene
      expression. In the animal study, the mice under chronic stress environment will be treated
      with NIR-tPBM of different duration. We will compare the behavioral differences relevant to
      anxiety, depression and cognitive performance, as well as the differences in neurogenesis,
      neuroplasticity, energy metabolism, circadian rhythm, and inflammation markers of the mice
      and the gene expression of the biomarkers. In both cellular and animal studies, dose-response
      assessment will be applied. In the clinical human study, we will conduct a prospective,
      double-blind, randomized, sham-controlled trial, recruiting totally 80 MDD patients, age 18
      to 75, and apply adjunctive NIR t-PBM to the dorsolateral prefrontal cortex, bilaterally and
      simultaneously, from 20 minutes and up to 80 minutes a day under the evaluation and
      recommendation of the clinicians, for 8 consecutive weeks. The change in depressive symptoms
      and circadian behaviors will be recorded in the 0, 2, 4, 8, 12 weeks and compared. The
      patient's peripheral blood-based biochemistry profile, inflammatory, oxidative stress, and
      circadian rhythm markers, as well as the gene expression of the relevant markers, will be
      collected in week 0, 8, and 12, and be compared.
    

Intervention name(s): NIR-tPBM; Sham device
Intervention type(s): Device; Device
Intervention description(s): The treatment will last for 8 weeks and be bilateral and applied to the frontal areas with one application site on the left side and one on the right side (left and right forehead centered on the frontal eminences and per EEG sites on F3 and F4). Energy is administered with a radiation wavelength of 830 nm. The duration of irradiation is from 20 minutes at each application site (the 2 sites are irradiated at the same time which is equivalent to 20 minutes of total time) to 40 minutes at each site, up to 2 times per day. The treatment will follow these specifications: PBM (IR) irradiance of 33.2 mW/cm2, each treatment window area is 28.7 cm2; PBM (IR) fluence of up to 60 Joules/cm2; energy delivered per session per device up to 1.72 kJ for a total of up to 3.44 kJ.; The sham device is completely identical in appearance, but only emits neglectable energy to the brain.
Other intervention name(s): near-infrared transcranial photobiomodulation; Sham
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: near-infrared radiation-transcranial photobiomodulation; circadian rhythm; Inflammation; Brain energy metabolism