NCT04619121

Near-infrared Radiation-transcranial Photobiomodulation for Major Depressive Disorder

Near-infrared Radiation-transcranial Photobiomodulation for Major Depressive Disorder: From Cellular, Animal Studies to a Sham-controlled Double-blind Randomized Clinical Trial

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: China Medical University Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Major Depressive Disorder
• Oxidative Stress

Interventions

Type	Name	Description
DEVICE	NIR-tPBM	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.
DEVICE	Sham device	The sham device is completely identical in appearance, but only emits neglectable energy to the brain.

Timeline

• Start date: 2020-12-21
• Primary completion: 2022-05-31
• Completion: 2022-07-31
• First posted: 2020-11-06
• Last updated: 2023-01-04

Locations

1 site across 1 country: Taiwan