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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Depression, Major Depressive Disorder

Intervention / Treatment
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* Device: Transcranial Light Therapy
* Device: Sham Transcranial Light Therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcranial Light Therapy<br>Transcranial light therapy penetrates the skin and brain using light energy and, the light energy may activate under-stimulated brain regions. | Device: Transcranial Light Therapy<br>* Transcranial light therapy penetrates the skin and brain using light energy; this makes transcranial light therapy noninvasive. Transcranial light therapy may activate under-stimulated brain regions.<br>* Other names: Low Level Laser-Light Therapy, Photobiomodulation;|
| Sham Comparator: Sham Transcranial Light Therapy<br>For the sham group, The transcranial light therapy device uses nonpenetrating light emitting diode light energy. The sham controls for which participants improve from the actual transcranial light therapy treatment and which participants improve during the study for reasons other than the therapy | Device: Transcranial Light Therapy<br>* Transcranial light therapy penetrates the skin and brain using light energy; this makes transcranial light therapy noninvasive. Transcranial light therapy may activate under-stimulated brain regions.<br>* Other names: Low Level Laser-Light Therapy, Photobiomodulation;Device: Sham Transcranial Light Therapy<br>* The same device used for the actual transcranial light therapy is used as the sham device; The device, when set to sham, will mimic the actual transcranial light therapy; however, when set to sham the device does not emit skin and cranium penetrating light emitting diode light energy.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quick Inventory of Depressive Symptomatology-Phase 1 | This is a brief (16-item) clinician-rated inventory of core depressive symptoms such as sleep, depressed mood, appetite, concentration, suicidal ideation, interest, energy, psychomotor retardation or agitation. Scores range from 0-27, higher scores indicating greater depression severity. | 6 weeks - Sequential-parallel comparison design | 
| Quick Inventory of Depressive Symptomatology(QIDS)-Phase 2 | This is a brief (16-item) clinician-rated inventory of core depressive symptoms such as sleep, depressed mood, appetite, concentration, suicidal ideation, interest, energy, psychomotor retardation or agitation. Scores range from 0-27, higher scores indicating greater depression severity. | 6 weeks - Sequential-parallel comparison design | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale - 17 Items(Phase 1) | assessment of the patient's depressive symptoms, using a structured interview and defined anchor points. The Hamilton Depression Rating Scale aims to quantify the degree of depression in patients who already have a diagnosis of major depression. Score ranges from 0-52. Higher score indicates greater severity of depression. | 6 weeks - Sequential-parallel comparison design | 
| Hamilton Depression Rating Scale - 17 Items(Phase 2) | assessment of the patient's depressive symptoms, using a structured interview and defined anchor points. The Hamilton Depression Rating Scale aims to quantify the degree of depression in patients who already have a diagnosis of major depression. Score ranges from 0-52. Higher score indicates greater severity of depression. | 6 weeks - Sequential-parallel comparison design | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Major Depressive Disorder, Major Depressive Episode