Transcranial Photobiomodulation for the Treatment of Pediatric Depression

Study Overview
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Brief Summary
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An open label trial to assess the safety and efficacy of transcranial photobiomodulation (tPBM) in improving symptoms of depression in youth.

Detailed Description
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Pediatric depression is a prevalent and morbid disorder estimated to affect up to 12% of youth in the United States by the time they reach adolescence. Recent research has documented that even minor symptoms of depression as captured through the Child Behavior Checklist (CBCL) Anxiety/Depression scale are strongly associated with the subsequent development of major depression. While treatments with antidepressants and psychotherapy are available, antidepressants can be associated with adverse effects including manic activation and psychosocial interventions are costly and not wide available. This state of affairs supports the search for safe and effective alternative treatments. One such opportunity is transcranial LED therapy, also known as transcranial photobiomodulation (tPBM). The treatment consists of exposing the frontal brain to the tPBM bilaterally, which is hypothesized to enhance adenosine triphosphate (ATP) production in depressed subjects. tPBM is a non-ionizing electromagnetic wave. It is invisible, penetrates the skin and skull into brain tissue, is non-invasive, is minimally dissipated as thermal energy, and is mainly absorbed by specific chromophores. The benefits of tPBM are wavelength specific. A mitochondrial enzyme, the cytochrome c oxidase, is the primary chromophore for the tPBM, with a wavelength around 830 nm. The energy absorbed by the cytochrome c oxidase leads to increased ATP production through the respiratory chain. Ultimately, the increased ATP is thought to lead to increased energy metabolism for the cell, and it is hypothesized that a signaling cascade is activated promoting cellular plasticity and cytoprotection. These properties of the tPBM have led to novel therapeutic applications in psychiatry. A preliminary open label study in 10 depressed subjects has shown that the tPBM was safe, effective and well tolerated in depressed adults. Further research confirmed these findings and shown tPBM therapy to be a promising intervention for adults with MDD. However, whether this non-invasive intervention may be safe and effective in pediatric depression remains unknown. To this end the investigators propose a pilot study is to evaluate whether tPBM is safe and effective in the treatment of pediatric depression. This study will enroll 30 youth of both sexes 6-17 years with active symptoms of depression as assessed through elevated scores on the CBCL Anxiety/depression scale. Based on the adult literature, investigators hypothesize that it will be safe and effective in this population.

Official Title
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Detailed Protocol: Evaluation of Transcranial Photobiomodulation for the Treatment of Pediatric Depression: An Open-Label Pilot Study

Conditions
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Depression

Intervention / Treatment
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* Device: Transcranial Photobiomodulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female children aged 6- 17 years A CBCL T score of ≥ 60 on the Anxious/Depressed scale Current treatment with a psychotropic medication or psychological treatment will be allowed provided that no medication or psychological treatment changes occur during the study Exclusion Criteria: Clinically unstable current psychiatric conditions judged to be a serious safety risk to self or others such as active suicidal ideation, psychosis or mania Subjects with an unstable medical condition that requires clinical attention The subject has a significant skin condition at the procedure sites (i.e., hemangioma, scleroderma, psoriasis, rash, open wound or tattoo). Inadequate command of the English language History of neurological injury or disease Impaired intellectual capacity (clinically determined) 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 Investigator and his/her immediate family, defined as the investigator's spouse, parent, child, grandparent, or grandchild

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcranial Photobiomodulation<br>Transcranial Photobiomodulation--a noninvasive intervention in which near-infrared light (850 nanometer) is applied to forebrain. | Device: Transcranial Photobiomodulation<br>* Transcranial Photobiomodulation--a noninvasive intervention in which near-infrared light (850 nanometer) is applied to forebrain.<br>* Other names: Niraxx G1 Headband;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy-Major Depressive Disorder (Clinical Global Impression - Major Depressive Disorder) | To evaluate the efficacy of transcranial photobiomodulation in treatment of depression. The Clinical Global Impression Scale rates symptoms of depression from a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients), with higher scores on this scale indicating a worse outcome. | Baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (The Transcranial Photobiomodulation Self-Report Questionnaire) | To assess the safety of transcranial photobiomodulation for treatment of depression. The Transcranial Photobiomodulation (tPBM) Self-Report Questionnaire rates the patient's comfort/discomfort with the tPBM on a scale of 0 (not discomfort) to 5 (extreme discomfort), with higher scores on this scale indicating a worse outcome. | Baseline to Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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light therapy, pediatric depression, depression, MDD