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Major Depressive DisorderTRIADENCT04366258

Transcranial Near Infrared Radiation and Cerebral Blood Flow in Depression

A study testing Transcranial Photobiomodulator in people with Major Depressive Disorder, run by NYU Langone Health at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Major Depressive Disorder
What is being tested?
Transcranial Photobiomodulator
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
55 participants
Where
3 sitesUnited States
Study dates
1 Aug 2020to 24 Jun 2022
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • Meeting diagnostic criteria for Major Depressive Disorder (MDD) in the past two weeks, at the DSM-5 Mini-International Neuropsychiatric Interview (MINI)
  • Inventory for Depressive Symptomatology Clinician-rated (IDS-C) total score ≥23 at screening
  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Massachusetts General Hospital

    Charlestown, Massachusetts, 02129

  • New York University

    New York, New York, 10016

  • Nathan Kline Institute

    Orangeburg, New York, 10962

Other trials in United States

About this study

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).

Read the 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.

Being tested
Transcranial Photobiomodulator, Sham
Keywords
MDD, neuromodulation, transcranial photobiomodulation
Medical subject headings
Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Transcranial PhotobiomodulatorDevice

    Also called LightForce® EXPi Deep Tissue Laser TherapyTM System, Transcranial PhotoBioModulation-1000 (tPBM-2.0)

    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).

  • ShamDevice

    Transcranial Photobiomodulator delivers sham irradiance dose of 0 mW/cm2.

Study groups in NCT04366258
Study groupRoleWhat they receive
Patients with MDDExperimentalParticipants will 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 (50 mW/cm2; 300 mW/cm2; 770 mW/cm2), as well as a sham dose (0 mW/cm2), once over the 4 treatment visits.
Receives: Device: Transcranial Photobiomodulator; Device: Sham

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During High-Irradiance t-PBM

    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.

    Measured: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

  2. Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During Middle-Irradiance t-PBM

    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.

    Measured: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

  3. Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During Low-Irradiance t-PBM

    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.

    Measured: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

  4. Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During Sham Treatment

    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.

    Measured: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

Secondary outcomes (14)
  1. Change in Brain Temperature During High-Irradiance t-PBM

    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.

    Measured: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7

  2. Change in Brain Temperature During Middle-Irradiance t-PBM

    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.

    Measured: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7

  3. Change in Brain Temperature During Low-Irradiance t-PBM

    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.

    Measured: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7

  4. Change in Brain Temperature During Sham Treatment

    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.

    Measured: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7

  5. Change in Columbia Suicide Severity Rating Scale (C-SSRS) Suicide Ideation Score

    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.

    Measured: Baseline, Follow-up (Week 8)

  6. Systematic Assessment for Treatment Emergent Events (SAFTEE) Score Prior to First Treatment

    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. The total score is the sum of responses. Scores range from 0 to 165; higher scores indicate greater severity of side effects

    Measured: Baseline

  7. Systematic Assessment for Treatment Emergent Events (SAFTEE) Score Following High-Irradiance t-PBM

    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. The total score is the sum of responses. Scores range from 0 to 165; higher scores indicate greater severity of side effects

    Measured: Immediately Post-Intervention, up to Week 7 in total

  8. Systematic Assessment for Treatment Emergent Events (SAFTEE) Score Following Middle-Irradiance t-PBM

    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. The total score is the sum of responses. Scores range from 0 to 165; higher scores indicate greater severity of side effects

    Measured: Immediately Post-Intervention, up to Week 7 in total

  9. Systematic Assessment for Treatment Emergent Events (SAFTEE) Score Following Low-Irradiance t-PBM

    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. The total score is the sum of responses. Scores range from 0 to 165; higher scores indicate greater severity of side effects

    Measured: Immediately Post-Intervention, up to Week 7 in total

  10. Systematic Assessment for Treatment Emergent Events (SAFTEE) Score Following Sham Treatment

    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. The total score is the sum of responses. Scores range from 0 to 165; higher scores indicate greater severity of side effects

    Measured: Immediately Post-Intervention, up to Week 7 in total

  11. t-PBM Self-Report Questionnaire (TSRQ) Score Following High-Irradiance t-PBM

    3-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 3-18; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.

    Measured: Immediately Post-Intervention, up to Week 7 in total

  12. t-PBM Self-Report Questionnaire (TSRQ) Score Following Middle-Irradiance t-PBM

    3-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 3-18; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.

    Measured: Immediately Post-Intervention, up to Week 7 in total

  13. t-PBM Self-Report Questionnaire (TSRQ) Score Following Low-Irradiance t-PBM

    3-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 3-18; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.

    Measured: Immediately Post-Intervention, up to Week 7 in total

  14. t-PBM Self-Report Questionnaire (TSRQ) Score Following Sham Treatment

    3-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 3-18; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.

    Measured: Immediately Post-Intervention, up to Week 7 in total

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2020
  2. Study start1 Aug 2020
  3. Primary completion30 Apr 2022
  4. Study completion24 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04366258
Sponsor's protocol ID
20-00217
Other IDs
1R61MH122647-01
Acronym
TRIADE
Status last verified
May 2023
First submitted
17 Apr 2020
Last updated
5 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Publications

  • Iosifescu DV, Collins KA, Tural U, Dmochowski JP, Gaggi N, Parincu Z, Peterson A, Hurtado-Puerto AM, Gersten MB, Clancy JA, McEachern KM, Sobeih T, de Taboada L, Tarpey T, Cassano P. Dose Dependent Effects of Transcranial Photobiomodulation on Blood-Oxygenation-Level-Dependent Power in Major Depressive Disorder. Brain Stimul. 2026 Aug 13:103185. doi: 10.1016/j.brs.2026.103185. Online ahead of print.

    PubMed 42595101

Questions about this trial

What is this clinical trial studying?

A study testing Transcranial Photobiomodulator in people with Major Depressive Disorder, run by NYU Langone Health at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04366258, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2023.

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