Transcranial Laser Therapy, Continuous and Pulsed Light, for Major Depressive Disorder (ELATED-3)

Transcranial Continuous and Pulse Near-Infrared Light in Depression: a Placebo-Controlled Study (ELATED-3).

Transcranial Light Therapy involves non-invasive and invisible beams of light that increase energy metabolism in the brain. Transcranial light therapy has been found to promote brain metabolism which may help people with depression. The research team proposes a novel approach to treating depression by using transcranial light therapy.

During study visits a clinician applies transcranial light therapy to both sides of a participant's forehead for about 30 minutes. The study involves, 1 screening visit which may last up to the 3 hours, 24 transcranial light therapy treatment visits, and 1 post-treatment visit (26 total visits to the Massachusetts General Hospital).

If a participant qualifies for the study, we assign the participant by chance to receive either active transcranial light therapy or sham transcranial light therapy treatment. During sham transcranial light therapy visits, the transcranial light therapy device will not produce near infrared waves (e.g., light energy that cannot penetrate the skin and cranium). Participants have an equal chance of being assigned to the active transcranial light therapy or the sham transcranial light therapy when first randomized. Neither the participant, nor the clinician, nor any research staff will know which study group the participant belongs.

Participants are randomized a second time after 6-weeks in the study. If the participant were in the sham group the first 6-weeks, that participant may receive the active transcranial light therapy treatment after re-randomization. If the participant were already in the active transcranial light therapy group during the first 6-weeks the participant continues receiving the active treatment. All in all, participants have a 1 in 3 chance of receiving the active transcranial light therapy treatment at some point during the study.

Inclusion Criteria:

• Participant age at screening will be between (>=)18 and 70 years old (inclusive).
• Participant meets the criteria for major depressive disorder
• Participants informed consent obtained in writing
• Participant is available to participate in the study for at least 12 weeks

Exclusion Criteria:

• Significant skin conditions near the application site
• Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment
• Recent history of stroke
• The participant failed more than 2 adequate treatment with Federal Drug Administration approved antidepressants during current episode per antidepressant treatment response questionnaire criteria (less than 50% decrease in depressive symptomatology).
• Structured psychotherapy focused on treating the subject's depression (i.e. cognitive behavioral therapy or interpersonal therapy) is permitted if started at least 8 weeks prior to the screening visit.
• Substance dependence or abuse in the past 3 months.
• History of a psychotic disorder or psychotic episode (current psychotic episode per M.I.N.I neuro-psychiatric assessment).
• Bipolar affective disorder (per M.I.N.I neuro-psychiatric assessment).
• Unstable medical illness, defined as any medical illness which is not well-controlled with standard-of-care medications (e.g., insulin for diabetes mellitus, hydrochlorothiazide for hypertension).
• Active suicidal or homicidal ideation (both intention and plan are present), as determined by Columbia Suicide Severity Rating Scale
• Cognitive impairment (Montreal Cognitive Assessment <21)
• The participant has a significant skin condition (i.e., hemangioma, scleroderma, psoriasis, rash, open wound or tattoo) on the subject's scalp that is found to be in proximity to any of the procedure sites.
• The subject has an implant of any kind in the head (e.g. stent, clipped aneurysm, embolised arteriovenous malformation, implantable shunt - Hakim valve).
• Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment (in US: Visudyne (verteporfin) - for age related macular degeneration; Aminolevulinic Acid- for actinic keratoses; Photofrin (porfimer sodium) - for esophageal cancer, non-small cell lung cancer; Levulan Kerastick (aminolevulinic acid hydrogen chloride) - for actinic keratosis; 5-aminolevulinic acid for non-melanoma skin cancer)
• Women of child-bearing potential must use a double-barrier method for birth control (e.g. condoms plus spermicide) if sexually active.