Major Depressive DisorderTRIADE-R33NCT05573074
Transcranial Near Infrared Radiation and Cerebral Blood Flow in Depression - R33
A study testing Transcranial Photobiomodulator in people with Major Depressive Disorder, run by NYU Langone Health at 3 sites in United States.
Trial summary
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. 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
- 120 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Apr 2023to 30 Jun 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 be 18-65 years of age
- 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
- Patients 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
- Met diagnostic criteria for an alcohol or substance use disorder, post-traumatic stress disorder, obsessive-compulsive disorder, anorexia nervosa, or bulimia nervosa within the preceding 6 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
- Cognitive impairment significant as determined by the Montreal Cognitive Assessment (MOCA) <22 or MOCA-Blind <19.
Show all 19Show 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, SNRIs, or Wellbutrin (bupropion).
- 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 (such as ECT, TMS, VNS); 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 v 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 hypersensitivity to tPBM.
- Significant skin conditions (i.e., hemangioma, scleroderma, psoriasis, rash, open wound or tattoo) 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 tPBM (e.g., stent, clipped aneurysm, embolized AVM, implantable shunt - Hakim valve).
- Failure to meet standard MRI safety requirements (e.g., claustrophobia, non-removable piercings, implanted medical devices, other non-removable metals) as determined by the MRI Safety Checklist.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Harvard Medical School
Boston, Massachusetts, 02114
Paolo Cassano, MD,PhD, 617-726-6421, PCASSANO@mgh.harvard.edu
Paolo Cassano, MD,PhD
- Recruiting
NYU Langone Health
New York, New York, 10016
Dan Iosifescu, MD, MSc, 646-754-5156, Dan.Iosifescu@nyulangone.org
Dan Iosifescu, MD, MSc
- Recruiting
Nathan Kline Institute for Psychiatric Research
Orangeburg, New York, 10962
Katherine A Collins, MSW, PhD, 845-398-6580, Kate.Collins@NKI.rfmh.org
Katerine A Collins, MSW, PhD
About this study
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.
Read the detailed description
In this multi-center study, approximately 60 subjects with Major Depressive Disorder (MDD) will undergo Magnetic Resonance Imaging (MRI) scanning during transcranial Photobiomodulation (tPBM) before and after a randomized, double-blinded, controlled 16 session course of treatment with tPBM or sham.
- Conditions
- Major Depressive Disorder
- Being tested
- Transcranial Photobiomodulator, Sham
- Keywords
- MDD, 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 tPBM-2.0
Transcranial photobiomodulator delivers Near-Infrared Radiation (NIR) continuous middle irradiance (291.7 mW/cm2) to patients' foreheads.
ShamDevice
Transcranial Photobiomodulator delivers sham irradiance odes of 0 mW/cm2
| Study group | Role | What they receive |
|---|---|---|
| tPBM Group | Experimental | 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) Receives: Device: Transcranial Photobiomodulator; Device: Sham |
| Sham Group | Active comparator | 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) Receives: Device: Transcranial Photobiomodulator; Device: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change of cerebral blood flow (CBF)
Cerebral blood flow (CBF) is measured as Blood oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflect changes in regional cerebral blood flow that delineates 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.
Measured: Baseline, Visit 18 (Week 10)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated on a 0-6 scale, resulting in a total score range of 0-60. The higher the score, the more severe the depression.
Measured: Baseline, Visit 17 (Week 9, endpoint)
Secondary outcomes (8)
Percent change of cerebral blood flow (CBF) at endpoint in relation to treatment outcome
Cerebral blood flow (CBF) is measured as Blood oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflect changes in regional cerebral blood flow that delineates 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. Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated on a 0-6 scale, resulting in a total score range of 0-60. The higher the score, the more severe the depression. MADRS change score from baseline to endpoint
Measured: Baseline, Visit 18 (Week 10)]
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated on a 0-6 scale, resulting in a total score range of 0-60. The higher the score, the more severe the depression.
Measured: Baseline, Visit 3 (Week 2)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated on a 0-6 scale, resulting in a total score range of 0-60. The higher the score, the more severe the depression.
Measured: Baseline, Visit 5 (Week 3)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated on a 0-6 scale, resulting in a total score range of 0-60. The higher the score, the more severe the depression.
Measured: Baseline, Visit 7 (Week 4)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated on a 0-6 scale, resulting in a total score range of 0-60. The higher the score, the more severe the depression.
Measured: Baseline, Visit 9 (Week 5)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated on a 0-6 scale, resulting in a total score range of 0-60. The higher the score, the more severe the depression.
Measured: Baseline, Visit 11 (Week 6)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated on a 0-6 scale, resulting in a total score range of 0-60. The higher the score, the more severe the depression.
Measured: Baseline, Visit 13 (Week 7)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated on a 0-6 scale, resulting in a total score range of 0-60. The higher the score, the more severe the depression.
Measured: Baseline, Visit 15 (Week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2022
- Study start1 Apr 2023
- Primary completion30 Apr 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Dan Iosifescu, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05573074
- Sponsor's protocol ID
- 22-01065
- Acronym
- TRIADE-R33
- Status last verified
- Feb 2026
- First submitted
- 6 Oct 2022
- Last updated
- 5 Feb 2026
- Results posted
- No
- 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
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Near Infrared Radiation and Cerebral Blood Flow in Depression - R33
- ClinicalTrials.gov ID
- NCT05573074
- Acronym / sponsor ID
- TRIADE-R33 / 22-01065
- Conditions
- Major Depressive Disorder
- Keywords
- MDD, transcranial Photobiomodulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 1 Apr 2023 (actual)
- Primary completion
- 30 Apr 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 10 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In this multi-center study, approximately 60 subjects with Major Depressive Disorder (MDD) will undergo Magnetic Resonance Imaging (MRI) scanning during transcranial Photobiomodulation (tPBM) before and after a randomized, double-blinded, controlled 16 session course of treatment with tPBM or sham.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tPBM Group | Experimental | Device: Transcranial Photobiomodulator, Device: ShamVisit 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) |
| Sham Group | Active comparator | Device: Transcranial Photobiomodulator, Device: ShamVisit 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) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Participants must be able to give written informed consent and follow study procedures
- Participants must be 18-65 years of age
- Participants must have major depressive disorder; all the following conditions need to be met to ensure presence of significant depression symptoms:
- 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.
Key exclusion criteria (19 listed)
- Unwilling or unable to comply with study requirements
- Patients 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
- Met diagnostic criteria for an alcohol or substance use disorder, post-traumatic stress disorder, obsessive-compulsive disorder, anorexia nervosa, or bulimia nervosa within the preceding 6 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial PhotobiomodulatorAlso: LightForce EXPi tPBM-2.0Transcranial photobiomodulator delivers Near-Infrared Radiation (NIR) continuous middle irradiance (291.7 mW/cm2) to patients' foreheads. | Device | Sham Group, tPBM Group |
| ShamTranscranial Photobiomodulator delivers sham irradiance odes of 0 mW/cm2 | Device | Sham Group, tPBM Group |
Primary outcome
Percent change of cerebral blood flow (CBF)
Time frame: Baseline, Visit 18 (Week 10)
Cerebral blood flow (CBF) is measured as Blood oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflect changes in regional cerebral blood flow that delineates 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.
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Time frame: Baseline, Visit 17 (Week 9, endpoint)
Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item is rated on a 0-6 scale, resulting in a total score range of 0-60. The higher the score, the more severe the depression.
8 secondary outcomes
Percent change of cerebral blood flow (CBF) at endpoint in relation to treatment outcome
Time frame: Baseline, Visit 18 (Week 10)]
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Time frame: Baseline, Visit 3 (Week 2)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Time frame: Baseline, Visit 5 (Week 3)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Time frame: Baseline, Visit 7 (Week 4)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Time frame: Baseline, Visit 9 (Week 5)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Time frame: Baseline, Visit 11 (Week 6)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Time frame: Baseline, Visit 13 (Week 7)
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) score
Time frame: Baseline, Visit 15 (Week 8)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dan Iosifescu, MD principal investigator
NYU Langone Health
3 sites in 1 country: see every site and its status.
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 8 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 5 Feb 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dan Iosifescu, MD (646-754-5156, Dan.Iosifescu@nyulangone.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change of cerebral blood flow (CBF) (time frame: Baseline, Visit 18 (Week 10)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Feb 2026; AzTrials last refreshed its copy on 8 Nov 2026.