Transcranial Laser Therapy for Major Depressive Disorder

Study Overview
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Brief Summary
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The purpose of this study is to see if using Transcranial LED Therapy (TLT) using the PhotoMedex's Omnilux NEw-U LED helps improve symptoms of major depressive disorder (MDD). TLT works by briefly delivering near-infrared (non-visible) radiations to the forehead. The radiations penetrate the brain and stimulate the cells & metabolism. Our goals are To assess the antidepressant effect of the TLT in depressed subjects. To assess the safety and tolerability of the TLT in depressed subjects To assess the acceptability of the TLT in depressed subjects To pilot test the impact on cognition of the TLT in depressed subjects (Ancillary Study)

Detailed Description
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TLT has previously been evaluated in two large studies of people who have had a stroke. To date, TLT has been administered to over 550 people who have had a stroke. TLT has also been used in 10 people with MDD who were taking part in a research study. During this study, TLT was shown to relieve MDD symptoms without causing too many side effects. The -Infrared Radiation (NIR) device is also marketed for wrinkles treatment, however it is experimental for the use in depression. An experimental device means that it is one that has not been approved by the U.S. Food and Drug Administration (FDA). During this study, the investigators hope to better find out if NIR TLT is helpful for treating depression. The investigators will do this by comparing the effects of TLT (active treatment) NIR device to a sham treatment (which is an inactive or pretend treatment) device. The sham (pretend) device looks exactly like the NIR device but will not use a near-infrared radiation during the study visits. There are two sets of identical devices that will be used in this study, producing active and sham treatment, respectively. The devices work exactly the same when you are receiving active treatment and sham treatment, except that the devices will produce therapeutic transcranial LED energy during the active treatment sessions but it will not produce this LED energy during the sham treatment sessions. The investigators hope to enroll about 30 subjects in this study at the Massachusetts General Hospital Depression Clinical and Research Program.

Official Title
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Evaluation of LED Therapeutic Effect in Depression (ELATED): a Placebo-Controlled, Parallel Study of Efficacy, Tolerability and Acceptability of a Novel Approach in the Community

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: Near-infrared radiation via Transcranial LED Therapy
* Device: Sham device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is at least 18 years of age at screening, but has not had their 66th birthday. SCID diagnosis of major depressive disorder (Structured Clinical Interview for Diagnostic Statistical Manual-IV) HAM-D-17 >14 and < 25 Women of child-bearing potential must use a double-barrier method for birth control (e.g. condoms with spermicide) if sexually active. Subject Informed Consent obtained in writing in compliance with local regulations prior to enrollment into this study. The subject (and caregiver, if applicable) is willing to participate in this study for at least 8 weeks. Subjects on an antidepressant will need to be on a stable dose for at least six weeks. Exclusion Criteria: The subject is pregnant or lactating. The subject failed two or more FDA-approved antidepressants during current episode Subjects with less than 2 months MDD symptom free prior to current episode. The subject used targeted psychotherapies for depression during current episode (support therapy or counseling are allowed) Substance dependence or abuse in the past 6 months Psychotic disorder or psychotic episode (current psychotic episode per SCID assessment) Bipolar affective disorder (per SCID assessment) Unstable medical illness, defined as any medical illness which has not been well-controlled with standard-of-care medications (e.g., insulin for diabetes mellitus, HCTZ for hypertension) Active suicidal or homicidal ideation, as determined by CHRT screening The subject 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 directly below any of the procedure sites. The subject has an implant of any kind in the head (e.g. stent, clipped aneurysm, embolised AVM, implantable shunt - Hakim valve). Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment (in US: Visudine (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 HCl) - for actinic keratosis; 5-aminolevulinic acid (ALA)- for non-melanoma skin cancer)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TLT Treatment Group 1<br>The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks | Device: Near-infrared radiation via Transcranial LED Therapy<br>* The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.<br>* Other names: Near-infrared radiation (NIR);|
| Sham Comparator: TLT Treatment Group 2<br>The sham group will receive 2 treatments of the sham device per week for 8 weeks | Device: Sham device<br>* The sham device does not emit near-infrared radiation.<br>* Other names: PhotoMedex Omnilux New-U.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Depression Rating Scale (HAM-D 17) Score | We anticipate that TLT will decrease HAM-D17 scores in study subjects significantly more than Sham treatment. We expect that we will be also able to estimate the effect size of the antidepressant action of TLT. Analyses were done for all evaluable subjects (participants who met the a priori cut-off of a minimum of 4 t-PBM sessions for inclusion in the study analyses) and treatment completers (participants followed for the entire 8-week study period and who received a clinical assessment immediately after). HAM-D17 questions are rated on a scale of 0-4 or 0-2 (total score: 0-50) with higher scores indicating more severe pathology. Scores typically fall into the following ranges: not depressed = 0-7; mildly depressed = 8-13; moderately depressed = 14-18; severely depressed = 19-22; very severely depressed = 23 and over. For the pilot study, we analyzed subjects from Baseline to Week 8. A last observation carried forward (LOCF) was performed to account for one week 8n missing value. | Visit 1 (Baseline) and Visit 17 (Week 9); Pilot Phase: Visit 1 (Baseline) and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systematic Assessment for Treatment Emergent Events-systematic Inquiry (SAFTEE-SI) | To assess the safety and tolerability of TLT in depressed subjects: We predict that TLT will be safe and well-tolerated, as assessed by the SAFTEE-SI. We anticipate no significant differences between TLT and Sham in side-effects.The SAFTEE is a commonly used instrument developed by the NIMH and adapted into a self-report instrument. The version we used is the same used by the NIMH-sponsored CO-MED trial. It examines all possible treatment-emergent side effects and adverse symptoms, including suicidal thoughts and behaviors, and self-injurious behavior. The SAFTEE analyses are ongoing and will be reported in a second paper (they are not included in the primary outcomes paper). The single value analyzed is the total number of distinct treatment-emergent side-effects (a side effect is defined as any item on the SAFTEE for which severity increased by two or more levels from baseline to any visit) that occurred for each subject. Range: 0 to 165; higher values represent worse outcomes. | Assessed at odd-numbered Visits 1-17. The single value to be analyzed is the number of distinct side effects that occurred at least once during these assessment visits for each subject. | 
| Number of Participants With Adverse Events | To assess the safety and tolerability of the TLT in depressed subjects: We predict that the TLT will be safe and well-tolerated by depressed patients, as assessed by the following rating scales: ADVERSE EVENTS FORM. We anticipate no significant differences in between TLT and Sham treatment as concerns side-effects. Due to the small sample size and the variability of reported adverse events, we decided that descriptive reporting (i.e. reporting each subject's adverse events individually) was more appropriate than analysis. All adverse events were reported in the adverse events section. In the outcome measure data table below we report the number of participants in each group who experienced an adverse event. | Visits 1, 3, 5, 7, 9, 11, 13, 15, and 17 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Device study, Depression, Major Depression, Major Depressive Disorder, MDD, Device for depression, Alternatives to medication for depression, Massachusetts General Hospital, Boston