Transcranial Near Infrared Radiation and Cerebral Blood Flow in Depression (TRIADE)

• ClinicalTrials.gov Identifier: NCT04366258
• Recruitment Status: Completed
• First Posted: April 28, 2020
• Last Update Posted: October 25, 2022
• Sponsor: NYU Langone Health
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): NYU Langone Health

Tracking Information

• First Submitted Date: April 17, 2020
• First Posted Date: April 28, 2020
• Last Update Posted Date: October 25, 2022
• Actual Study Start Date: August 1, 2020
• Actual Primary Completion Date: April 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 21, 2022)

• Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) during High-Irradiance t-PBM [ Time Frame: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7 ]
  CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans. Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.
• Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) during Middle-Irradiance t-PBM [ Time Frame: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7 ]
  CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans. Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.
• Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) during Low-Irradiance t-PBM [ Time Frame: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7 ]
  CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans. Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.
• Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) during Sham Treatment [ Time Frame: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7 ]
  CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans. Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.

Original Primary Outcome Measures (submitted: April 27, 2020)

Change of t-PBM effects on Blood Oxygen Level Dependent (BOLD) signal [ Time Frame: 12 weeks ]

The specificity of t-PBM effects on Blood Oxygen Level Dependent(BOLD) signal increases will be assessed by testing three irradiance doses covering a wide range (50, 300 and 700 mW/cm2) versus sham. If a reliable effect on BOLD (compared to sham, the BOLD increase at the optimal dose will have an effect size of Cohen's d≥0.5) is seen with PBM, the study validate BOLD fMRI as a robust biomarker of target engagement for t-PBM and act as a "go" signal. In contrast, if none of the t-PBM doses yield reliable BOLD increases, this will fail the putative mechanism (no go).

Current Secondary Outcome Measures (submitted: October 21, 2022)

• Change in Brain Temperature during High-Irradiance t-PBM [ Time Frame: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7 ]
  Changes computed using data recorded with magnetic resonance (MR) thermometry scans taken immediately before and after the 20-minute transcranial photobiomodulation (t-PBM) treatment administration.
• Change in Brain Temperature during Middle-Irradiance t-PBM [ Time Frame: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7 ]
  Changes computed using data recorded with magnetic resonance (MR) thermometry scans taken immediately before and after the 20-minute transcranial photobiomodulation (t-PBM) treatment administration.
• Change in Brain Temperature during Low-Irradiance t-PBM [ Time Frame: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7 ]
  Changes computed using data recorded with magnetic resonance (MR) thermometry scans taken immediately before and after the 20-minute transcranial photobiomodulation (t-PBM) treatment administration.
• Change in Brain Temperature during Sham Treatment [ Time Frame: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7 ]
  Changes computed using data recorded with magnetic resonance (MR) thermometry scans taken immediately before and after the 20-minute transcranial photobiomodulation (t-PBM) treatment administration.
• Change in Columbia Suicide Severity Rating Scale (C-SSRS) Suicide Ideation Score [ Time Frame: Baseline, Follow-up (Week 8) ]
  C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) to 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation. Any score greater than 0 is important and may indicate the need for mental health intervention.
• Systematic Assessment for Treatment Emergent Events (SAFTEE) Score following High-Irradiance t-PBM [ Time Frame: Up to Week 7 ]
  55-item self-assessment measuring severity levels of side effects. Participants rank each item on a 4-point Likert scale ranging from 0-3, where: 0 = None; 1 = Mild; 2 = Moderate; and 3 = Severe. Scores range from 0 to 165; higher scores indicate greater severity of side effects
• Systematic Assessment for Treatment Emergent Events (SAFTEE) Score following Middle-Irradiance t-PBM [ Time Frame: Up to Week 7 ]
  55-item self-assessment measuring severity levels of side effects. Participants rank each item on a 4-point Likert scale ranging from 0-3, where: 0 = None; 1 = Mild; 2 = Moderate; and 3 = Severe. Scores range from 0 to 165; higher scores indicate greater severity of side effects
• Systematic Assessment for Treatment Emergent Events (SAFTEE) Score following Low-Irradiance t-PBM [ Time Frame: Up to Week 7 ]
  55-item self-assessment measuring severity levels of side effects. Participants rank each item on a 4-point Likert scale ranging from 0-3, where: 0 = None; 1 = Mild; 2 = Moderate; and 3 = Severe. Scores range from 0 to 165; higher scores indicate greater severity of side effects
• Systematic Assessment for Treatment Emergent Events (SAFTEE) Score following Sham Treatment [ Time Frame: Up to Week 7 ]
  55-item self-assessment measuring severity levels of side effects. Participants rank each item on a 4-point Likert scale ranging from 0-3, where: 0 = None; 1 = Mild; 2 = Moderate; and 3 = Severe. Scores range from 0 to 165; higher scores indicate greater severity of side effects
• t-PBM Self-Report Questionnaire (TSRQ) Score following High-Irradiance t-PBM [ Time Frame: Up to Week 7 ]
  5-item self-report assessment of potential inconveniences and discomforts from the transcranial photobiomodulation (t-PBM). Participants rank each item on various Likert scales. The total score is the sum of responses. Total score ranges from 5-21; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.
• t-PBM Self-Report Questionnaire (TSRQ) Score following Middle-Irradiance t-PBM [ Time Frame: Up to Week 7 ]
  5-item self-report assessment of potential inconveniences and discomforts from the transcranial photobiomodulation (t-PBM). Participants rank each item on various Likert scales. The total score is the sum of responses. Total score ranges from 5-21; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.
• t-PBM Self-Report Questionnaire (TSRQ) Score following Low-Irradiance t-PBM [ Time Frame: Up to Week 7 ]
  5-item self-report assessment of potential inconveniences and discomforts from the transcranial photobiomodulation (t-PBM). Participants rank each item on various Likert scales. The total score is the sum of responses. Total score ranges from 5-21; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.
• t-PBM Self-Report Questionnaire (TSRQ) Score following Sham Treatment [ Time Frame: Up to Week 7 ]
  5-item self-report assessment of potential inconveniences and discomforts from the transcranial photobiomodulation (t-PBM). Participants rank each item on various Likert scales. The total score is the sum of responses. Total score ranges from 5-21; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.

Original Secondary Outcome Measures (submitted: April 27, 2020)

• Changes in the frequency of suicidal ideation experienced [ Time Frame: 4 visits over 4-8 weeks ]
  This will be measured by the Columbia Suicide Severity Rating Scale (C-SSRS), an instrument endorsed by the FDA for clinical trials. This instrument systematically tracks suicidal ideation and behavior. The C-SSRS is made up of ten categories, all of which maintain binary responses (yes/no) to indicate a presence or absence of the behavior. A yes/no binary response is also utilized in assessing self-injurious behavior without suicidal intent. The results of scoring will indicate the following: Suicidal ideation "Yes" Categories 1-5, Suicidal behavior "Yes" Categories 6-10 and Suicidal ideation & behavior "Yes" Categories 1-10
• Change in overall depression severity [ Time Frame: 4 visits over 4-8 weeks ]
  This will be measured by the use of Clinical Global Impressions - Severity (CGI-S). This instrument is scored 1-7 by the clinician based on assessment of the subject's overall clinical status. It will measure, based on history and scores on other instruments the overall depressive severity (CGI-S). The score of 1 indicates normal where as the score of 7 indicates extremely ill patients.
• Change in overall clinical improvement [ Time Frame: 4 visits over 4-8 weeks ]
  This will be assessed by using the Clinical Global Impressions - Improvement (CGI-I). The instrument is scored 1-7 by the clinician based on assessment of the subject's overall clinical status. It will measure, based on history and scores on other instruments the overall clinical improvement (CGI-I). The score of 1 indicates very much improved whereas the score of 7 indicates very much worse in clinical status
• Effectiveness of Blinding Process [ Time Frame: 4 visits over 4-8 weeks ]
  The effectiveness of the blinding process in this study will be assessed by the Perceptions of Blinding Questionnaire (PBQ). The PBQ is a self-report questionnaire to determine the degree to which the participant believes s/he is receiving the treatment or the sham.
• Change in the frequency of side effects experienced [ Time Frame: 4 visits over 4-8 weeks ]
  This will be measured by using the Systematic Assessment for Treatment Emergent Events (SAFTEE). The SAFTEE is a commonly used instrument originally developed by NIMH and adapted into a self-report instrument. This version of the scale examines in a systematic fashion all possible treatment-emergent side effects and probes specific adverse symptoms, including suicidal thoughts and behaviors, and self-injurious behavior.
• Changes in frequency of self reported side effects of t-PBM [ Time Frame: 4 visits over 4-8 weeks ]
  This will be measured by the t-PBM Self-Report Questionnaire (TSRQ). An open-ended questionnaire focusing on potential inconveniences and discomforts from the t-PBM administered after each experimental visit.

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: April 27, 2020)

• Change in depression severity in participants [ Time Frame: 4 visits over 4-8 weeks ]
  This will be measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). This 10-item clinician-rated instrument measures depression severity. It will be administered with a structured interview guide. The time frame for this scale is the past 7 days. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.
• Change in participants with symptoms of depression [ Time Frame: 4 visits over 4-8 weeks ]
  This will be measured by the Symptoms of Depression Questionnaire (SDQ). This is a comprehensive measure of depression that includes the assessment of symptoms in the anxiety-depression spectrum. It assesses irritability, anger attacks, and anxiety symptoms together with the commonly considered symptoms of depression. Analysis of the factor structure of the SDQ identified 5 subscales, including one in the anxiety-depression spectrum, with adequate internal consistency and concurrent validity.
• Change in anxiety severity in participants [ Time Frame: 4 visits over 4-8 weeks ]
  This will be measured with Anxiety Symptoms Questionnaire (ASQ). This is a 17-item self-report questionnaire measuring the frequency and intensity of 17 symptoms of anxiety, including nervousness, worrying, irritability, trouble relaxing, insomnia, lack of energy, difficulty concentrating, somatic symptoms, and impairment in functioning due to anxiety.
• Change in the Participants' perceived quality of cognition [ Time Frame: 4 visits over 4-8 weeks ]
  This will be assessed with the Quality of Life in Neurological Disorders, Cognitive Section (Neuro-QoL). The cognitive section of the Neuro-QoL is an 8 item self-rated measure of both executive function and general concerns. It measures perceived difficulties in cognitive abilities (e.g., memory, attention, and decision making) or in the application of such abilities to everyday tasks (e.g., planning, organizing, calculating, remembering and learning).
• Change in Participants' perceived quality of life [ Time Frame: 4 visits over 4-8 weeks ]
  This is assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF). Participants rate their satisfaction with the following domains of activity: physical health, feelings, work, household duties, school/course work, leisure time activities, and social relations. Each item uses a 5-point scale ranging from 1 (very poor) to 5 (very good). A total score is derived from 14 items with a maximum score of 70 and with higher scores indicating greater life satisfaction and enjoyment.

Descriptive Information

• Brief Title: Transcranial Near Infrared Radiation and Cerebral Blood Flow in Depression
• Official Title: Transcranial Near Infrared Radiation and Cerebral Blood Flow in Depression
• Brief Summary: This study will compare the effect of three transcranial photobiomodulation (t-PBM) doses (high, middle, and low irradiance) to sham t-PBM on PFC CBF as assessed with fMRI (BOLD) in this multi-center, phase I, double-blinded, dose-ranging, controlled, crossover study of 30 subjects with MDD. All eligible participants will undergo four sessions of t-PBM during fMRI so that they experience irradiances of 50, 300 and 700 mW/cm2 as well as sham. The order of dose administration will be randomized and t-PBM will be administered with the LightForce® EXPi Deep Tissue Laser TherapyTM System, Transcranial PhotoBioModulation-1000 (tPBM-2.0).
• Detailed Description: The purpose of this research study is to determine if application of near infrared energy to the forehead can change blood flow in the brains of people with depression. Near infrared energy is like light but is not visible to the human eye. This research study will compare near infrared exposure with a placebo or sham procedure. The sham procedure will look and feel just like the near infrared procedure but won't include near infrared exposure.
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

four sessions of t-PBM during fMRI, each session will occur, in random order, with t-PBM irradiances of 50, 300 and 700 mW/cm2 as well as sham.

Masking: Double (Participant, Investigator)
Primary Purpose: Diagnostic

• Condition: Major Depressive Disorder

Intervention

• Device: Transcranial Photobiomodulator
  Delivers laser-generated Near-Infrared Radiation (NIR) to forehead at 3 doses of irradiance - High (770 mW/cm2), Middle (300 mW/cm2), and Low (50 mW/cm2).
  Other Name: LightForce® EXPi Deep Tissue Laser TherapyTM System, Transcranial PhotoBioModulation-1000 (tPBM-2.0)
• Device: Sham
  Transcranial Photobiomodulator delivers sham irradiance dose of 0 mW/cm2.

Study Arms

• Experimental: t-PBM at Low Irradiance, then t-PBM at Middle Irradiance, then t-PBM at High Irradiance, then Sham

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 4: Sham irradiance dose of 0 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Low Irradiance, then t-PBM at High Irradiance, then t-PBM at Middle Irradiance, then Sham

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 4: Sham irradiance dose of 0 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Middle Irradiance, then t-PBM at High Irradiance, then t-PBM at Low Irradiance, then Sham

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 4: Sham irradiance dose of 0 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Middle Irradiance, then t-PBM at Low Irradiance, then t-PBM at High Irradiance, then Sham

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 4: Sham irradiance dose of 0 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at High Irradiance, then t-PBM at Low Irradiance, then t-PBM at Middle Irradiance, then Sham

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 4: Sham irradiance dose of 0 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at High Irradiance, then t-PBM at Middle Irradiance, then t-PBM at Low Irradiance, then Sham

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 4: Sham irradiance dose of 0 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Low Irradiance, then t-PBM at Middle Irradiance, then Sham, then t-PBM at High Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 3: Sham irradiance dose of 0 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 770 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Low Irradiance, then t-PBM at High Irradiance, then Sham, then t-PBM at Middle Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 3: Sham irradiance dose of 0 mW/cm2
  • Visit 4: t-PBM at irradiance doses of 300 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Middle Irradiance, then t-PBM at Low Irradiance, then Sham, then t-PBM at High Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 3: Sham irradiance dose of 0 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 770 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Middle Irradiance, then t-PBM at High Irradiance, then Sham, then t-PBM at Low Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 3: Sham irradiance dose of 0 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 50 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at High Irradiance, then t-PBM at Middle Irradiance, then Sham, then t-PBM at Low Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 3: Sham irradiance dose of 0 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 50 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at High Irradiance, then t-PBM at Low Irradiance, then Sham, then t-PBM at Middle Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 3: Sham irradiance dose of 0 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 300 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Low Irradiance, then Sham, then t-PBM at Middle Irradiance, then t-PBM at High Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 2: Sham irradiance dose of 0 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 770 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Low Irradiance, then Sham, then t-PBM at High Irradiance, then t-PBM at Middle Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 2: Sham irradiance dose of 0 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 300 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Middle Irradiance, then Sham, then t-PBM at Low Irradiance, then t-PBM at High Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 2: Sham irradiance dose of 0 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 770 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at Middle Irradiance, then Sham, then t-PBM at High Irradiance, then t-PBM at Low Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 2: Sham irradiance dose of 0 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 50 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at High Irradiance, then Sham, then t-PBM at Middle Irradiance, then t-PBM at Low Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 2: Sham irradiance dose of 0 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 50 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: t-PBM at High Irradiance, then Sham, then t-PBM at Low Irradiance, then t-PBM at Middle Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 2: Sham irradiance dose of 0 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 300 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: Sham, then t-PBM at Low Irradiance, then t-PBM at Middle Irradiance, then t-PBM at High Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: Sham irradiance dose of 0 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 770 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: Sham, then t-PBM at Low Irradiance, then t-PBM at High Irradiance, then t-PBM at Middle Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: Sham irradiance dose of 0 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 300 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: Sham, then t-PBM at Middle Irradiance, then t-PBM at Low Irradiance, then t-PBM at High Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: Sham irradiance dose of 0 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 770 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: Sham, then t-PBM at Middle Irradiance, then t-PBM at High Irradiance, then t-PBM at Low Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: Sham irradiance dose of 0 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 50 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: Sham, then t-PBM at High Irradiance, then t-PBM at Middle Irradiance, then t-PBM at Low Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: Sham irradiance dose of 0 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 300 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 50 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham
• Experimental: Sham, then t-PBM at High Irradiance, then t-PBM at Low Irradiance, then t-PBM at Middle Irradiance

  Participants undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose, including a sham dose, once over the 4 treatment visits.

  Schedule of interventions:

  • Visit 1: Sham irradiance dose of 0 mW/cm2
  • Visit 2: t-PBM at irradiance dose of 770 mW/cm2
  • Visit 3: t-PBM at irradiance dose of 50 mW/cm2
  • Visit 4: t-PBM at irradiance dose of 300 mW/cm2
  Interventions:

  • Device: Transcranial Photobiomodulator
  • Device: Sham

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 28, 2022): 56
• Original Estimated Enrollment (submitted: April 27, 2020): 30
• Actual Study Completion Date: June 24, 2022
• Actual Primary Completion Date: April 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants must be able to give written informed consent and follow study procedures

• Participants must have major depressive disorder; all the following conditions need to be met to ensure presence of significant depression symptoms:

  1. Meeting diagnostic criteria for Major Depressive Disorder (MDD) in the past two weeks, at the DSM-5 Mini-International Neuropsychiatric Interview (MINI)
  2. Inventory for Depressive Symptomatology Clinician-rated (IDS-C) total score ≥23 at screening
  3. Depression symptoms are the primary target of treatment or treatment-seeking.
• Women of child-bearing potential must agree to use adequate contraception
• Participants taking medications or psychotherapy approved for the treatment of major depressive disorder will need to be stable for at least 8 weeks prior to screen

Exclusion Criteria:

• Unwilling or unable to comply with study requirements
• Participants who are judged to be at serious and imminent suicidal (C-SSRS≥4) or homicide risk, or currently in crisis such that inpatient hospitalization or other crisis management should take priority
• History of any or psychotic or bipolar disorder
• Alcohol or substance use disorder, post-traumatic stress disorder, obsessive-compulsive disorder and eating disorders within the preceding 12 months
• History of dementia, traumatic brain injury (TBI), or neurological disorders affecting the brain, including any history of stroke or seizure disorders requiring treatment in the last 5 years (even if controlled with medications)
• Cognitive impairment significant as determined by the Montreal Cognitive Assessment (MOCA) <22
• History of antisocial personality disorder, or any clinically significant personality trait that would, in the investigator's judgment, preclude safe study participation or impair ability to remain adherent with the treatment protocol.
• History of significant treatment non-adherence or situations where the subjects are unlikely to adhere to treatment, in the opinion of the investigator
• Pregnant (as confirmed by pregnancy test at screen) or nursing.
• Currently undergoing device-based treatment for depression or taking medications for depression other than SSRIs or SNRIs.
• Treatment resistance with failure to respond to more than two adequate treatments with FDA-approved antidepressant medications during current episode of major depressive disorder.
• History of ECT in the last 12 months; lifetime history of VNS; lifetime treatment resistance to any FDA-approved device-based treatment for major depressive disorder; device-based interventions for depression will need to be discontinued at least 8 weeks prior to screen.
• Serious, unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, hematologic disease; defined as any medical illness which is not well-controlled with standard-of-care medications
• Clinically significant abnormal findings of laboratory parameters including urine toxicology screen for drugs of abuse or at physical examination
• Clinical or laboratory evidence of uncontrolled hypothyroidism; if maintained on thyroid medication must be euthyroid for at least 1 month before screening.
• Past intolerance or hypersensivity to t-PBM.
• Significant skin conditions on the subject's scalp that are found in the area of the procedure sites.
• Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment.
• Any type of implants in the head, whose functioning might be affected by t-PBM.
• Failure to meet standard MRI safety requirements as determined by the MRI Safety Checklist.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04366258
• Other Study ID Numbers: 20-00217; 1R61MH122647-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data and upon reasonable request. Requests should be directed to Dr. Kate Collins, PhD (email: Kate.Collins@nki.rfmh.org). To gain access, data requestors will need to sign a data access agreement.

• Current Responsible Party: NYU Langone Health
• Original Responsible Party: Same as current
• Current Study Sponsor: NYU Langone Health
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Dan Iosifescu, MD; NYU Langone Health

• PRS Account: NYU Langone Health
• Verification Date: July 2022