Transcranial Photobiomodulation for Depression

(TRIADE-R33 Trial)

Recruiting at 2 trial locations

Overseen By Anna Peterson

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must be taking: SSRIs, SNRIs, Wellbutrin

Must not be taking: Antidepressants, others

Disqualifiers: Bipolar, Substance use, Neurological, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

Duration: 10 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a special kind of invisible light aimed at the forehead to help people with depression. The light might improve blood flow in the brain. About 60 people with depression will be part of this study to see if this treatment works.

Will I have to stop taking my current medications?

The trial requires that participants taking medications for depression must be stable on their current medications for at least 8 weeks before screening. If you are taking medications other than SSRIs, SNRIs, or Wellbutrin (bupropion), you may need to stop them.

What data supports the effectiveness of the treatment Transcranial Photobiomodulation for Depression?

Research suggests that transcranial photobiomodulation (tPBM) may help reduce depressive symptoms, as shown in a meta-analysis where it decreased depression severity. However, more studies are needed to confirm its effectiveness compared to a placebo. ^{1 2 3 4 5}

Is transcranial photobiomodulation safe for humans?

Transcranial photobiomodulation (tPBM) is generally considered safe, with studies showing no serious adverse events. Some mild side effects may occur, but they usually resolve without needing to stop treatment. ^{2 3 5 6 7}

How does transcranial photobiomodulation treatment differ from other treatments for depression?

Transcranial photobiomodulation (tPBM) is a unique, non-invasive treatment that uses near-infrared light to stimulate brain activity, unlike traditional depression treatments that often involve medication or talk therapy. It is considered low risk and inexpensive, but its effectiveness compared to placebo is still under investigation, with some studies showing promising results. ^{1 2 3 4 5}

Research Team

Dan Iosifescu, MD, MSc

Principal Investigator

NYU Langone Health

Eligibility Criteria

Adults aged 18-65 with Major Depressive Disorder, stable on current medications or psychotherapy for at least 8 weeks, and not in immediate crisis. They must score ≥23 on the IDS-C for depression severity and be able to consent to study procedures. Excludes those with certain psychiatric disorders, substance abuse issues, significant medical conditions, or using specific depression treatments.

Inclusion Criteria

I have been on a stable treatment for depression for at least 8 weeks.

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.

I am seeking treatment mainly for my depression symptoms.

Exclusion Criteria

I haven't had ECT in the past year, VNS ever, or been resistant to device-based depression treatments.

My thyroid condition is stable, and I've been on medication for at least a month.

I am using a device or taking non-SSRI/SNRI/Wellbutrin medication for depression.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 16-session course of transcranial Photobiomodulation (tPBM) or sham treatment

10 weeks

19 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sham
• Transcranial Photobiomodulator

Trial Overview The trial is testing if near infrared energy applied to the forehead can alter brain blood flow in depressed individuals. Participants will either receive the actual Transcranial Photobiomodulator treatment or a sham (placebo) procedure to compare effects.

Participant Groups

Group I: tPBM Group Experimental Treatment 2 Interventions

Visit 1: t-PBM at irradiance dose of 291.7 mW/cm2 (333s) Visit 2 - 18: randomized to receive active t-PBM of 291.7 mW/cm2 (333s) Visit 19: t-PBM at irradiance dose of 291.7 mW/cm2 (333s)

Group II: Sham Group Active Control 2 Interventions

Visit 1: t-PBM at irradiance does of 291.7 mW/cm2 (333s) Visit 2 - 18: randomized to receive Sham of 0 mW/cm2 (333s) Visit 19: t-PBM at irradiance dose of 291.7 mW/cm2 (333s)

Transcranial Photobiomodulator is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Photobiomodulation Therapy for:

• Depression (investigational)
• Traumatic Brain Injury (investigational)
• Stroke (investigational)
• Breast Cancer Related Lymphedema (investigational)

Approved in European Union as Transcranial Photobiomodulation Therapy for:

• No specific approvals listed; various investigational uses

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

Photobiomodulation (PBM) using red and near-infrared light shows promise as a low-risk treatment for major depressive disorder (MDD), with studies indicating significant antidepressant effects comparable to traditional medications.

The proposed mechanism of action involves enhancing mitochondrial metabolism in brain cells, suggesting that PBM could improve brain function, although more research is needed to determine optimal treatment parameters and confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial and systemic photobiomodulation for major depressive disorder: A systematic review of efficacy, tolerability and biological mechanisms. Caldieraro, MA., Cassano, P.[2019]

Transcranial photobiomodulation (tPBM) is a safe and non-invasive treatment that effectively enhances higher electrophysiological oscillations in the brain, based on a review of 10 studies involving healthy individuals aged 18-80.

While tPBM shows promise in improving brain activity, the evidence regarding its effects on lower oscillatory frequencies remains inconclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of transcranial photobiomodulation on electrophysiological activity of brain in healthy individuals: A scoping review. Shetty, SJ., Shetty, S., Shettigar, D., et al.[2023]

Transcranial photobiomodulation (tPBM) shows promise in reducing depressive symptoms, with a significant effect size found in a meta-analysis of eight studies, indicating its potential as a treatment for major depressive disorder (MDD).

However, the evidence from double-blind, sham-controlled studies did not show a significant advantage of tPBM over sham treatment, suggesting that further research with larger sample sizes and optimized treatment parameters is necessary to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Transcranial Photobiomodulation on Depressive Symptoms: A Meta-Analysis. Cho, Y., Tural, U., Iosifescu, DV.[2023]

In a study involving 20 individuals, those receiving near-infrared transcranial photobiomodulation (NIR t-PBM) showed a significant improvement in sexual function compared to those receiving sham therapy, indicating its potential efficacy for treating sexual dysfunction.

The improvements in sexual function were not linked to the antidepressant effects of t-PBM, suggesting that NIR t-PBM may have a distinct therapeutic action specifically for sexual dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of transcranial photobiomodulation with near-infrared light on sexual dysfunction. Cassano, P., Dording, C., Thomas, G., et al.[2020]

In a study involving 49 participants with major depressive disorder (MDD), transcranial photobiomodulation (t-PBM) using low irradiance and low energy did not show significant efficacy compared to sham treatment, indicating that the current dosing may be insufficient for therapeutic effects.

The results suggest that a minimal dose threshold is necessary for t-PBM to be effective in treating MDD, similar to other neuromodulation techniques, highlighting the need for further research to determine optimal dosing parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very Low-Level Transcranial Photobiomodulation for Major Depressive Disorder: The ELATED-3 Multicenter, Randomized, Sham-Controlled Trial. Iosifescu, DV., Norton, RJ., Tural, U., et al.[2022]

Transcranial photobiomodulation (t-PBM) using near-infrared light showed significant antidepressant effects in patients with major depressive disorder (MDD), with effect sizes ranging from 0.90 to 1.5 based on different analysis methods over an 8-week treatment period.

The treatment was well tolerated with no serious adverse events reported, suggesting it is a safe adjunct therapy for MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial. Cassano, P., Petrie, SR., Mischoulon, D., et al.[2021]

In a study involving 18 participants with major depressive disorder, repeated sessions of near-infrared transcranial photobiomodulation (t-PBM) showed a trend towards more side effects compared to a sham treatment, but these were generally mild and resolved during the study.

The treatment did not lead to significant changes in weight or blood pressure, although a slight increase in diastolic blood pressure was noted, indicating that the overall safety profile of repeated t-PBM sessions appears to be benign.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reported Side Effects, Weight and Blood Pressure, After Repeated Sessions of Transcranial Photobiomodulation. Cassano, P., Caldieraro, MA., Norton, R., et al.[2020]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial and systemic photobiomodulation for major depressive disorder: A systematic review of efficacy, tolerability and biological mechanisms. [2019]

2. Scotland pubmed.ncbi.nlm.nih.gov

Effect of transcranial photobiomodulation on electrophysiological activity of brain in healthy individuals: A scoping review. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Transcranial Photobiomodulation on Depressive Symptoms: A Meta-Analysis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of transcranial photobiomodulation with near-infrared light on sexual dysfunction. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Very Low-Level Transcranial Photobiomodulation for Major Depressive Disorder: The ELATED-3 Multicenter, Randomized, Sham-Controlled Trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Reported Side Effects, Weight and Blood Pressure, After Repeated Sessions of Transcranial Photobiomodulation. [2020]