Trial of Transcranial Photobiomodulation for Depression With PET and EEG Outcomes

NCT06934135 | Completed FDA Device

• 1 other identifier: NITLT01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Major depressive disorder (MDD) is a leading cause of disability worldwide, and many patients do not achieve adequate benefit from current treatments. Transcranial photobiomodulation (tPBM) is a non-invasive neuromodulation technique that delivers near-infrared (808 nm) light through the scalp to frontal brain regions involved in mood regulation. Preclinical and early clinical studies suggest that tPBM may improve symptoms of depression and enhance cortical function. This randomized, sham-controlled, parallel-group trial evaluates the efficacy, safety, and neural effects of tPBM in adults with MDD. Participants are assigned to one of four groups: high-dose continuous wave (CW), low-dose continuous wave (CW\_LOW), pulsed wave (PW), or sham treatment. Interventions are delivered 3 times a week for 6 weeks (total of 18 sessions) to bilateral frontal scalp sites (AF3 and AF4). The primary outcome is change in depressive symptoms measured by the Hamilton Depression Rating Scale (HAMD-17) from baseline to week 18. Secondary outcomes include changes in self-reported depression scales (QIDS, SDQ), regional brain glucose metabolism measured by FDG-PET, and resting-state EEG markers. Safety and tolerability are assessed throughout the trial, including adverse events, scalp/site reactions, and suicidality screening. This study will provide proof-of-concept evidence for the clinical efficacy and mechanistic effects of tPBM in major depression and will inform the design of larger, multicenter clinical trials.

Conditions

Depression; Depression, Anxiety; Depressive Disorder; Depressive Disorder, Major

Keywords

Depression, Major Depressive Disorder, Photobiomodulation; FDG-PET, EEG; Near-Infrared Light Therapy, Brain Metabolism; Neurostimulation, Mental Health, Non-Invasive Therapy

Outcome Measures

Primary Outcomes (1)

• Effect on depressive symptoms

  The primary outcome is change in depressive symptom severity in patients with Major Depressive Disorder (MDD), comparing three active doses of near-infrared transcranial light therapy (NIR-TLT) and Sham. Symptoms are measured using the 17-item Hamilton Depression Rating Scale (HAMD-17).

  Baseline, mid-treatment (Week 3), post-treatment (Week 6), and at 2-week follow-up (Week 8).

Secondary Outcomes (1)

• Secondary Outcome Measures

  QIDS-SR16 and SDQ: baseline, mid-treatment (Week 3), and post-intervention (Week 6), EEG: baseline, mid-treatment (Week 3), and post-intervention (Week 6), FDG-PET: baseline and post-intervention (Week 6).

Other Outcomes (1)

• Other Pre-Specified Outcomes

  Minimally at baseline, mid-treatment (Week 3), and end of treatment (Week 6).

Study Arms (4)

Arm A - Experimental: Continuous Wave (CW, High Dose)

EXPERIMENTAL

Participants receive bilateral tPBM at EEG sites AF3 and AF4 using 808 nm near-infrared light, continuous wave mode. Average irradiance is \~350 mW/cm² (≈4.2 W over two 12 cm² beams). Treatments are delivered twice weekly for 9 weeks (18 sessions total). 429 seconds, 3 times a week for 6 weeks. Delivering to to the brain a total of 3.6 kJ/session, and \~65 kJ/procedure.

Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)

Arm B - Experimental: Continuous Wave Low Dose (CW_LOW)

EXPERIMENTAL

Participants receive bilateral tPBM at AF3 and AF4 using 808 nm light in continuous wave mode at reduced average irradiance (\~50 mW/cm²; \~1.2 W total). Each 429-second session, three times per week for 6 weeks (18 sessions), delivers \~0.52 kJ/session and \~9.3 kJ total.

Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)

Arm C - Experimental: Pulsed Wave (PW)

EXPERIMENTAL

Participants receive bilateral tPBM at AF3 and AF4 using 808 nm light delivered in pulsed mode (42 Hz, 33% duty cycle). Peak irradiance \~1050 mW/cm²; average \~350 mW/cm² (\~8.4 W total). Each 429-second session, three times per week for 6 weeks (18 sessions), delivers \~3.6 kJ/session and \~65 kJ total.

Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)

Arm D - Sham Comparator: Sham tPBM

SHAM COMPARATOR

Participants receive sham stimulation at AF3 and AF4 with an identical-appearing device that emits no therapeutic light. Session length (429 seconds), frequency (3×/week for 6 weeks), and procedures are matched to active arms to maintain blinding.

Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)

Interventions

Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) DEVICE

The system delivers 808 nm near-infrared light via fiber optics through a headset forming \~12 cm² beams at EEG sites AF3/AF4 (dorsolateral prefrontal cortex). Participants are randomized to: (1) Continuous Wave (CW, high dose) \~350 mW/cm² (\~8.4 W total); (2) Continuous Wave Low Dose (CW\_LOW) \~50 mW/cm² (\~1.2 W); (3) Pulsed Wave (PW) peak \~1050 mW/cm², 42 Hz, 33% duty cycle (avg \~350 mW/cm²); or (4) Sham device with identical cues but no light. Sessions last 429 s, 3×/week for 6 weeks (18 total). Sham matches duration/procedures. Outcomes include depressive symptoms (HAMD-17, QIDS, SDQ), FDG-PET, and EEG.

Also known as: SHAM (Placebo), NIR-TLT

Arm A - Experimental: Continuous Wave (CW, High Dose); Arm B - Experimental: Continuous Wave Low Dose (CW_LOW); Arm C - Experimental: Pulsed Wave (PW); Arm D - Sham Comparator: Sham tPBM

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The age of subjects in the study will be between 18 and 75 years (inclusive). Diagnosis of Major Depressive Disorder (MINI). QIDS-C ≥12 at screening. CGI-S ≥4 or higher, i.e., "moderately depressed." Women of childbearing potential must use a double-barrier method of birth control (e.g., condoms plus spermicides) if sexually active.
• Written informed consent was obtained from the subject in accordance with local regulations prior to enrollment in this study.
• The subject is willing to participate in this study for at least 12 weeks. Subjects must have been on stable doses of antidepressants (if taking any) for at least six weeks before enrollment.

You may not qualify if:

• A decrease in self-reported SDQ from screening to baseline ≥30%, calculated as \[((SDQ\_screening-88) - (SDQ\_baseline-88)) / (SDQ\_screening-88)\] ≥30/100. A score of 88 is considered "normal" on the SDQ.
• The subject is pregnant or breastfeeding. The subject has failed more than 2 adequate treatments with FDA-approved antidepressants during the current episode according to ATRQ criteria (less than a 50% reduction in depressive symptoms).
• Structured psychotherapy focused on treating depression (i.e., CBT or IPT) is allowed if initiated at least 8 weeks before the screening visit.
• Substance dependence or abuse in the past 3 months. History of a psychotic disorder or psychotic episode (current psychotic episode as per MINI evaluation).
• Bipolar affective disorder (as determined by MINI evaluation). Unstable medical illness, is defined as any medical condition that is not well controlled with standard care medications (e.g., insulin for diabetes mellitus, HCTZ for hypertension).
• Active suicidal or homicidal ideation (both intent and plan are present), as determined by C-SSRS screening.
• The subject has a significant skin condition (e.g., hemangioma, scleroderma, psoriasis, rash, open wound, or tattoo) on the scalp near any of the procedure sites.
• The subject has any type of implant in the head (e.g., stent, clipped aneurysm, embolized AVM, implantable shunt - Hakim valve).
• Any use of light-activated medications (photodynamic therapy) within 14 days prior to study enrollment (in the U.S.: Visudyne (verteporfin) - for age-related macular degeneration; Aminolevulinic Acid - for actinic keratosis; Photofrin (porfimer sodium) - for esophageal cancer, non-small cell lung cancer; Levulan Kerastick (aminolevulinic acid HCl) - for actinic keratosis; 5-aminolevulinic acid (ALA) - for non-melanoma skin cancer).
• Recent history of stroke (within 90 days). The subject had a failed intervention with an FDA-approved device for depression treatment during the current episode (e.g., less than a 50% reduction in depressive symptoms with TMS, ECT, or VNS).
• History of dementia, traumatic brain injury (TBI), or any other organic neurological disorder.

Sponsors & Collaborators

• NeuroThera DE: lead
• Peruvian Clinical Research: collaborator

Study Sites (2)

Clinica Vesalio

Lima, 15036, Peru

Location

Hospital Nacional Guillermo Almenara Irigoyen

Lima, L01, Peru

Location

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MeSH Terms

Conditions

Depression; Anxiety Disorders; Depressive Disorder; Depressive Disorder, Major; Psychological Well-Being

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mental Disorders; Mood Disorders; Personal Satisfaction

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, care providers, investigators, outcome assessors (those evaluating the results), and the sponsor are blinded to the group assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This randomized, double-blind, sham-controlled, parallel-group trial evaluates the effects of transcranial photobiomodulation (tPBM) on depressive symptoms, brain function, and safety in adults with Major Depressive Disorder (MDD). About 60 participants are randomized to one of four arms: high-dose continuous wave (CW, \~350 mW/cm²), low-dose CW (\~50 mW/cm²), pulsed wave (PW, peak \~1050 mW/cm²; 42 Hz, 33% duty cycle), or sham. Treatments are delivered 3×/week for 6 weeks (18 sessions) bilaterally over frontal EEG sites AF3/AF4 using 808 nm NIR light (\~12 cm² beams). The primary outcome is change in HAMD-17 (at baseline, mid, and post-treatment). Secondary outcomes include QIDS-SR16, SDQ, safety metrics, EEG biomarkers (at baseline, mid, and post-treatment), and FDG-PET (baseline and post-treatment) in a 20-participant substudy. The study assesses both clinical efficacy and neural mechanisms of action.

Study Record Dates

• First Submitted: April 11, 2025
• First Posted: April 18, 2025
• Study Start: August 24, 2022
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

PE (2)