Trial of Transcranial Photobiomodulation for Depression With PET and EEG Outcomes (NITLT01)

April 10, 2026 updated by: NeuroThera DE

Randomized, Sham-Controlled Trial of Transcranial Photobiomodulation for Major Depressive Disorder With PET and EEG Biomarker Outcomes.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This randomized, sham-controlled, parallel-group clinical trial evaluates the efficacy and safety of transcranial photobiomodulation (tPBM) for adults with major depressive disorder (MDD). Participants are randomly assigned in equal proportions to one of four intervention arms:

  1. CW (Continuous Wave, high dose): 808 nm near-infrared laser light delivered continuously at an average irradiance of ~350 mW/cm².
  2. CW_LOW (Continuous Wave, low dose): 808 nm laser light delivered continuously at an average irradiance of ~50 mW/cm².
  3. PW (Pulsed Wave): 808 nm laser light delivered in pulsed mode at a peak irradiance of ~1050 mW/cm², frequency 42 Hz, with 33% duty cycle.
  4. SHAM (Placebo control): Identical headset with no therapeutic light emission, producing only background cues to preserve blinding.

Treatments are administered twice weekly for 9 consecutive weeks (18 sessions total). Each session consists of bilateral application to frontal scalp locations AF3 and AF4 (10-20 EEG system), using circular beams of ~12 cm² per site. The device incorporates standardized positioning and timing protocols to ensure reproducibility across participants.

PET Substudy: A subset of 20 participants undergo 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging at baseline (V0) and post-treatment (V18). Following intravenous tracer injection, participants rest quietly for ~30 minutes prior to scanning. During the uptake and imaging period, participants receive a sequence of 10 minutes of simulated treatment, 10 minutes of their randomized intervention (CW, CW_LOW, PW, or SHAM), and 10 minutes of simulated treatment. The primary PET region of interest is the dorsolateral prefrontal cortex (DLPFC); additional cortical and limbic regions are examined in exploratory analyses.

EEG Assessments: Resting-state electroencephalography (EEG) is recorded at V0, V9, and V18 to evaluate spectral power (delta, theta, alpha, beta bands) and connectivity indices.

Safety Assessments: Safety and tolerability are evaluated at every visit, including collection of adverse events (AEs), serious adverse events (SAEs), scalp/site tolerability ratings (e.g., erythema, discomfort), suicidality screening with the Columbia Suicide Severity Rating Scale (C-SSRS), and reasons for discontinuation.

Hypotheses: The primary hypothesis is that CW tPBM will result in a significantly greater reduction in depressive symptom severity (HAMD-17 total score) compared with SHAM at week 18. Secondary hypotheses include improvement in QIDS and SDQ scores, increased FDG-PET metabolism in DLPFC, and normalization of EEG markers.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Peru
      • Lima, Peru, 15036
        • Clinica Vesalio
      • Lima, Peru, L01
        • Hospital Nacional Guillermo Almenara Irigoyen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A - Experimental: Continuous Wave (CW, High Dose)
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)
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.
Other Names:
  • SHAM (Placebo)
  • NIR-TLT
Experimental: Arm B - Experimental: Continuous Wave Low Dose (CW_LOW)
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)
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.
Other Names:
  • SHAM (Placebo)
  • NIR-TLT
Experimental: Arm C - Experimental: Pulsed Wave (PW)
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)
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.
Other Names:
  • SHAM (Placebo)
  • NIR-TLT
Sham Comparator: Arm D - Sham Comparator: Sham tPBM
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)
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.
Other Names:
  • SHAM (Placebo)
  • NIR-TLT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect on depressive symptoms
Time Frame: Baseline, mid-treatment (Week 3), post-treatment (Week 6), and at 2-week follow-up (Week 8).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Outcome Measures
Time Frame: 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).

Self-report symptom scales: Quick Inventory of Depressive Symptomatology (QIDS-SR16) and Symptoms of Depression Questionnaire (SDQ), measured at the same intervals.

Neurophysiological biomarkers:

Resting-state EEG. Spectral power (delta, theta, alpha, beta) and functional connectivity will be assessed.

Cerebral glucose metabolism via FDG-PET in a substudy of 20 participants. Primary Region of Interest (ROI): Frontal Lobe. Exploratory ROIs include other cortical/limbic regions.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Other Pre-Specified Outcomes
Time Frame: Minimally at baseline, mid-treatment (Week 3), and end of treatment (Week 6).

Composite clinical scores (e.g., Z-score averaging of HAMD-17 and QIDS)

Safety and tolerability metrics, including:

Adverse events (AEs) Serious adverse events (SAEs) Scalp/site tolerability (erythema, discomfort) Suicidality assessments using the Columbia-Suicide Severity Rating Scale (C-SSRS)
Minimally at baseline, mid-treatment (Week 3), and end of treatment (Week 6).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NeuroThera DE

Collaborators

Peruvian Clinical Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 24, 2022

Primary Completion (Actual)

August 1, 2025

Study Completion (Actual)

August 1, 2025

Study Registration Dates

First Submitted

April 11, 2025

First Submitted That Met QC Criteria

April 11, 2025

First Posted (Actual)

April 18, 2025

Study Record Updates

Last Update Posted (Actual)

April 15, 2026

Last Update Submitted That Met QC Criteria

April 10, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NITLT01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Not available at the moment

Drug and device information, study documents

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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