NCT06934135

Trial of Transcranial Photobiomodulation for Depression With PET and EEG Outcomes

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: NeuroThera DE · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Depression
• Depression, Anxiety
• Depressive Disorder
• Depressive Disorder, Major

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2022-08-24
• Primary completion: 2025-08-01
• Completion: 2025-08-01
• First posted: 2025-04-18
• Last updated: 2026-04-15

Locations

2 sites across 1 country: Peru

Regulatory

• FDA-regulated device study