DepressionELATED-4NCT06934135
Near-infrared Transcranial Laser Therapy in Subjects With Major Depressive Disorder
A study testing Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) in people with Depression and Depressive Disorder, run by NeuroThera DE at 2 sites in Peru.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Depression, Depressive Disorder, Depressive Disorder, Major
- What is being tested?
- Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 2 sitesPeru
- Study dates
- 24 Aug 2022to 1 Aug 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- A decrease in self-reported SDQ from screening to baseline ≥30%, calculated as [((SDQscreening-88) - (SDQbaseline-88)) / (SDQscreening-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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
Peru2 sites
Clinica Vesalio
Lima, Lima Province, 15036
Hospital Nacional Guillermo Almenara Irigoyen
Lima, Lima Province, L01
About this study
Official title: Near-infrared Transcranial Laser Therapy in Subjects With Major Depressive Disorder: A Study of Dosing With Laser.
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: Continuous Wave, Medium Dose (CW), Continuous Wave, Low Dose (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/F3 and AF4/F4).
Read more
The primary outcome is change in depressive symptoms measured by the Hamilton Depression Rating Scale (HAMD-17) from baseline to the end of treatment (Week 6, Visit 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.
Read the 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:
- CW (Continuous Wave, Medium Dose): 808 nm near-infrared laser delivered continuously at an irradiance of 300 mW/cm².
- CW_LOW (Continuous Wave, Low Dose): 808 nm near-infrared laser delivered continuously at an irradiance of 50 mW/cm².
- PW (Pulsed Wave): 808 nm near-infrared laser delivered at an average irradiance of 300 mW/cm². Pulse parameters include a frequency of 42 Hz and a duty cycle of 33%, resulting in a peak irradiance of 900 mW/cm².
- SHAM: Identical device without therapeutic light emission. Irradiance = 0 mW/cm².
Treatments are administered three times per week for six consecutive weeks, for a total of 18 treatment sessions. Each treatment session consists of bilateral application to frontal scalp regions corresponding to AF3/F3 and AF4/F4 exposure sites. Each exposure area measures 12 cm², with both sites irradiated simultaneously for 429 seconds per session.
PET Substudy: A subset of 20 participants underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging at baseline (V0) and post-treatment (V18). Following intravenous tracer injection, participants rested quietly for approximately 30 minutes before scanning. Each 30-minute imaging session comprised three consecutive 10-minute acquisition blocks: Block A (no light), Block B (during which 429 seconds of tPBM or sham was delivered according to randomized assignment), and Block C (no light). Blocks A and C were light-free in every arm. The primary PET region of interest was the frontal lobe; the secondary region of interest was the dorsolateral prefrontal cortex (DLPFC); additional cortical and limbic regions were examined in exploratory analyses.
EEG Assessments: Resting-state electroencephalography (EEG) was recorded at V1, 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 6/Visit 18. Secondary hypotheses include improvement in QIDS and SDQ scores, increased FDG-PET metabolism in the frontal lobe, and normalization of EEG markers.
- Conditions
- Depression, Depressive Disorder, Depressive Disorder, Major
- Being tested
- Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)
- Keywords
- Depression, Major Depressive Disorder, Photobiomodulation, FDG-PET, EEG, Near-Infrared Light Therapy, Brain Metabolism, Neurostimulation, Mental Health, Non-Invasive Therapy
- Medical subject headings
- Depression, Depressive Disorder, Depressive Disorder, Major, Psychological Well-Being
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)Device
Also called NIR-TLT
808-nm near-infrared laser light is delivered through a headset forming approximately uniform, round beams of approximately 12 cm² at each of 2 bilateral frontal scalp sites (EEG positions AF3/F3 and AF4/F4; approximately 24 cm² total), irradiated simultaneously. Arms: (1) CW, Medium Dose, approximately 300 mW/cm² average irradiance (3.6 W per site; 7.2 W both sites); (2) CW_LOW, approximately 50 mW/cm² (0.6 W per site; 1.2 W both sites); (3) PW, 42 Hz, 33% duty cycle, peak approximately 900 mW/cm² (10.8 W per site; 21.6 W both sites), average approximately 300 mW/cm² (3.6 W per site; 7.2 W both sites); (4) Sham, identical device and procedural cues, no therapeutic emission (0 mW/cm²). Sessions lasted 429 seconds, 3 times weekly for 6 weeks (18 sessions). Sham duration and procedures matched the active arms to maintain blinding.
| Study group | Role | What they receive |
|---|---|---|
| Arm A - Experimental: Continuous Wave (CW, Medium Dose) | Experimental | Participants receive bilateral tPBM with 808-nm near-infrared light delivered in continuous-wave mode simultaneously to two scalp sites, centered over EEG positions AF3/F3 and AF4/F4. A diffractive optical element produces a near-uniform, round beam of approximately 12 cm² at each site (approximately 24 cm² total irradiated area). Average irradiance is approximately 300 mW/cm², corresponding to approximately 3.6 W of optical power per site and approximately 7.2 W for both sites combined. Each session lasts 429 seconds, delivering approximately 129 J/cm² per site, approximately 1.54 kJ per site, and approximately 3.09 kJ per session for both sites combined. Treatments are administered 3 times weekly for 6 weeks (18 sessions total), for a cumulative exposure of approximately 2.32 kJ/cm² per site, approximately 27.8 kJ per site, and approximately 55.6 kJ for both sites combined over the entire treatment course. Receives: Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) |
| Arm B - Experimental: Continuous Wave Low Dose (CW_LOW) | Experimental | Participants receive bilateral 808-nm continuous-wave tPBM over AF3/F3 and AF4/F4 through two round beams of approximately 12 cm² each (approximately 24 cm² total). Average irradiance is approximately 50 mW/cm², corresponding to approximately 0.6 W per site and approximately 1.2 W for both sites combined. Each 429-second session delivers approximately 21.5 J/cm² per site, approximately 0.26 kJ per site, and approximately 0.51 kJ for both sites combined. Over 18 sessions (3 times weekly for 6 weeks), cumulative exposure is approximately 386 J/cm² per site, approximately 4.6 kJ per site, and approximately 9.3 kJ for both sites combined. Receives: Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) |
| Arm C - Experimental: Pulsed Wave (PW) | Experimental | Participants receive bilateral 808-nm tPBM in pulsed mode over AF3/F3 and AF4/F4, using the same two round beams of approximately 12 cm² each (approximately 24 cm² total) and the same 429-second session duration as the other active arms. Light is pulsed at 42 Hz with a 33% duty cycle (pulse period approximately ~24 ms; approximately ~8 ms ON and approximately 16 ms OFF; approximately 18,000 pulses per session). Peak irradiance is approximately 900 mW/cm², corresponding to approximately 10.8 W peak optical power per site and approximately 21.6 W peak for both sites combined. Time-averaged irradiance is approximately 300 mW/cm², corresponding to approximately 3.6 W average per site and approximately 7.2 W average for both sites combined, matched to Arm A. Delivered energy is therefore identical to Arm A. This arm isolates waveform (pulsed vs continuous) at matched average irradiance and matched total delivered energy. Receives: Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) |
| Arm D - Sham Comparator: Sham tPBM | Sham comparator | Participants undergo identical procedures with an identical-appearing device positioned over AF3/F3 and AF4/F4 that emits no therapeutic near-infrared light (0 mW/cm², 0 W, and 0 J at each site and for both sites combined). Session duration (429 seconds), frequency (3 times weekly for 6 weeks, 18 sessions), device setup, operator contact, and all visible and audible device cues are matched to the active arms to maintain blinding. Because 808-nm light is invisible, no perceptual cue distinguishes active from sham emission. Receives: Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline, mid-treatment (Week 3), post-treatment (Week 6), and at 2-week follow-up (Week 8).
Secondary outcomes (1)
Secondary Outcome Measures
Self-report symptom scales: Quick Inventory of Depressive Symptomatology (QIDS-C) 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. Secondary ROI: dorsolateral prefrontal cortex (DLPFC). Exploratory ROIs include other cortical/limbic regions.
Measured: QIDS-C 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2025
- Study start24 Aug 2022
- Primary completion1 Aug 2025
- Study completion1 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (60)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This randomized, sham-controlled, parallel-group study evaluated the effects of transcranial photobiomodulation (tPBM) in adults with major depressive disorder (MDD). Fifty participants were randomized to one of four groups: Continuous Wave, Medium Dose (CW, 300 mW/cm²), Continuous Wave, Low Dose (CW\_LOW, 50 mW/cm²), Pulsed Wave (PW; average irradiance 300 mW/cm², peak irradiance 900 mW/cm², 42 Hz, 33% duty cycle), or Sham. Treatments were administered three times weekly for six weeks (18 sessions total) using 808-nm near-infrared light delivered bilaterally and simultaneously to frontal scalp sites AF3/F3 and AF4/F4. The primary outcome measure was change in HAMD-17 score. Secondary outcomes included QIDS-C, SDQ, safety assessments, EEG biomarkers, and FDG-PET imaging in a substudy of 20 participants. The study evaluated both clinical efficacy and neural mechanisms of action.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- NeuroThera DE
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Peruvian Clinical Research
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06934135
- Sponsor's protocol ID
- NITLT01
- Acronym
- ELATED-4
- Status last verified
- Sep 2026
- First submitted
- 11 Apr 2025
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Zivin JA, Albers GW, Bornstein N, Chippendale T, Dahlof B, Devlin T, Fisher M, Hacke W, Holt W, Ilic S, Kasner S, Lew R, Nash M, Perez J, Rymer M, Schellinger P, Schneider D, Schwab S, Veltkamp R, Walker M, Streeter J; NeuroThera Effectiveness and Safety Trial-2 Investigators. Effectiveness and safety of transcranial laser therapy for acute ischemic stroke. Stroke. 2009 Apr;40(4):1359-64. doi: 10.1161/STROKEAHA.109.547547. Epub 2009 Feb 20.
PubMed 19233936Zhang Q, Ma H, Nioka S, Chance B. Study of near infrared technology for intracranial hematoma detection. J Biomed Opt. 2000 Apr;5(2):206-13. doi: 10.1117/1.429988.
PubMed 10938785Yu W, Naim JO, McGowan M, Ippolito K, Lanzafame RJ. Photomodulation of oxidative metabolism and electron chain enzymes in rat liver mitochondria. Photochem Photobiol. 1997 Dec;66(6):866-71. doi: 10.1111/j.1751-1097.1997.tb03239.x.
PubMed 9421973Yamaura M, Yao M, Yaroslavsky I, Cohen R, Smotrich M, Kochevar IE. Low level light effects on inflammatory cytokine production by rheumatoid arthritis synoviocytes. Lasers Surg Med. 2009 Apr;41(4):282-90. doi: 10.1002/lsm.20766.
PubMed 19347944Xu Z, Guo X, Yang Y, Tucker D, Lu Y, Xin N, Zhang G, Yang L, Li J, Du X, Zhang Q, Xu X. Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mice. Mol Neurobiol. 2017 Aug;54(6):4551-4559. doi: 10.1007/s12035-016-9983-2. Epub 2016 Jul 5.
PubMed 27379735Wu X, Alberico SL, Moges H, De Taboada L, Tedford CE, Anders JJ. Pulsed light irradiation improves behavioral outcome in a rat model of chronic mild stress. Lasers Surg Med. 2012 Mar;44(3):227-32. doi: 10.1002/lsm.22004. Epub 2012 Feb 14.
PubMed 22334326Thomson, D. J. (1982). Spectrum estimation and harmonic analysis. Proceedings of the IEEE, 70(9), 1055-1096.
Simon NM, McNamara K, Chow CW, Maser RS, Papakostas GI, Pollack MH, Nierenberg AA, Fava M, Wong KK. A detailed examination of cytokine abnormalities in Major Depressive Disorder. Eur Neuropsychopharmacol. 2008 Mar;18(3):230-3. doi: 10.1016/j.euroneuro.2007.06.004. Epub 2007 Aug 3.
PubMed 17681762Schiffer F, Johnston AL, Ravichandran C, Polcari A, Teicher MH, Webb RH, Hamblin MR. Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety. Behav Brain Funct. 2009 Dec 8;5:46. doi: 10.1186/1744-9081-5-46.
PubMed 19995444Shelton RC, Claiborne J, Sidoryk-Wegrzynowicz M, Reddy R, Aschner M, Lewis DA, Mirnics K. Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Mol Psychiatry. 2011 Jul;16(7):751-62. doi: 10.1038/mp.2010.52. Epub 2010 May 18.
PubMed 20479761Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.
PubMed 9881538Salehpour F, Rasta SH, Mohaddes G, Sadigh-Eteghad S, Salarirad S. Therapeutic effects of 10-HzPulsed wave lasers in rat depression model: A comparison between near-infrared and red wavelengths. Lasers Surg Med. 2016 Sep;48(7):695-705. doi: 10.1002/lsm.22542. Epub 2016 Jul 1.
PubMed 27367569Salehpour F, Rasta SH. The potential of transcranial photobiomodulation therapy for treatment of major depressive disorder. Rev Neurosci. 2017 May 24;28(4):441-453. doi: 10.1515/revneuro-2016-0087.
PubMed 28231069Sacher J, Neumann J, Funfstuck T, Soliman A, Villringer A, Schroeter ML. Mapping the depressed brain: a meta-analysis of structural and functional alterations in major depressive disorder. J Affect Disord. 2012 Oct;140(2):142-8. doi: 10.1016/j.jad.2011.08.001. Epub 2011 Sep 3.
PubMed 21890211Rezin GT, Cardoso MR, Goncalves CL, Scaini G, Fraga DB, Riegel RE, Comim CM, Quevedo J, Streck EL. Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression. Neurochem Int. 2008 Dec;53(6-8):395-400. doi: 10.1016/j.neuint.2008.09.012. Epub 2008 Sep 27.
PubMed 18940214
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Near-infrared Transcranial Laser Therapy in Subjects With Major Depressive Disorder: A Study of Dosing With Laser.
- ClinicalTrials.gov ID
- NCT06934135
- Acronym / sponsor ID
- ELATED-4 / NITLT01
- Conditions
- Depression, 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- NeuroThera DEIndustry (pharma, biotech, devices)
- Collaborators
- Peruvian Clinical Research
- Study start
- 24 Aug 2022 (actual)
- Primary completion
- 1 Aug 2025 (actual)
- Study completion
- 1 Aug 2025 (actual)
- First posted
- 18 Apr 2025 (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.
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: Continuous Wave, Medium Dose (CW), Continuous Wave, Low Dose (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/F3 and AF4/F4).
The primary outcome is change in depressive symptoms measured by the Hamilton Depression Rating Scale (HAMD-17) from baseline to the end of treatment (Week 6, Visit 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:
- CW (Continuous Wave, Medium Dose): 808 nm near-infrared laser delivered continuously at an irradiance of 300 mW/cm².
- CW_LOW (Continuous Wave, Low Dose): 808 nm near-infrared laser delivered continuously at an irradiance of 50 mW/cm².
- PW (Pulsed Wave): 808 nm near-infrared laser delivered at an average irradiance of 300 mW/cm². Pulse parameters include a frequency of 42 Hz and a duty cycle of 33%, resulting in a peak irradiance of 900 mW/cm².
- SHAM: Identical device without therapeutic light emission. Irradiance = 0 mW/cm².
Treatments are administered three times per week for six consecutive weeks, for a total of 18 treatment sessions. Each treatment session consists of bilateral application to frontal scalp regions corresponding to AF3/F3 and AF4/F4 exposure sites. Each exposure area measures 12 cm², with both sites irradiated simultaneously for 429 seconds per session.
PET Substudy: A subset of 20 participants underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging at baseline (V0) and post-treatment (V18). Following intravenous tracer injection, participants rested quietly for approximately 30 minutes before scanning. Each 30-minute imaging session comprised three consecutive 10-minute acquisition blocks: Block A (no light), Block B (during which 429 seconds of tPBM or sham was delivered according to randomized assignment), and Block C (no light). Blocks A and C were light-free in every arm. The primary PET region of interest was the frontal lobe; the secondary region of interest was the dorsolateral prefrontal cortex (DLPFC); additional cortical and limbic regions were examined in exploratory analyses.
EEG Assessments: Resting-state electroencephalography (EEG) was recorded at V1, 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 6/Visit 18. Secondary hypotheses include improvement in QIDS and SDQ scores, increased FDG-PET metabolism in the frontal lobe, and normalization of EEG markers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- This randomized, sham-controlled, parallel-group study evaluated the effects of transcranial photobiomodulation (tPBM) in adults with major depressive disorder (MDD). Fifty participants were randomized to one of four groups: Continuous Wave, Medium Dose (CW, 300 mW/cm²), Continuous Wave, Low Dose (CW_LOW, 50 mW/cm²), Pulsed Wave (PW; average irradiance 300 mW/cm², peak irradiance 900 mW/cm², 42 Hz, 33% duty cycle), or Sham. Treatments were administered three times weekly for six weeks (18 sessions total) using 808-nm near-infrared light delivered bilaterally and simultaneously to frontal scalp sites AF3/F3 and AF4/F4. The primary outcome measure was change in HAMD-17 score. Secondary outcomes included QIDS-C, SDQ, safety assessments, EEG biomarkers, and FDG-PET imaging in a substudy of 20 participants. The study evaluated both clinical efficacy and neural mechanisms of action.
| Arm | Type | Receives |
|---|---|---|
| Arm A - Experimental: Continuous Wave (CW, Medium Dose) | Experimental | Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)Participants receive bilateral tPBM with 808-nm near-infrared light delivered in continuous-wave mode simultaneously to two scalp sites, centered over EEG positions AF3/F3 and AF4/F4. A diffractive optical element produces a near-uniform, round beam of approximately 12 cm² at each site (approximately 24 cm² total irradiated area). Average irradiance is approximately 300 mW/cm², corresponding to approximately 3.6 W of optical power per site and approximately 7.2 W for both sites combined. Each session lasts 429 seconds, delivering approximately 129 J/cm² per site, approximately 1.54 kJ per site, and approximately 3.09 kJ per session for both sites combined. Treatments are administered 3 times weekly for 6 weeks (18 sessions total), for a cumulative exposure of approximately 2.32 kJ/cm² per site, approximately 27.8 kJ per site, and approximately 55.6 kJ for both sites combined over the entire treatment course. |
| Arm B - Experimental: Continuous Wave Low Dose (CW_LOW) | Experimental | Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)Participants receive bilateral 808-nm continuous-wave tPBM over AF3/F3 and AF4/F4 through two round beams of approximately 12 cm² each (approximately 24 cm² total). Average irradiance is approximately 50 mW/cm², corresponding to approximately 0.6 W per site and approximately 1.2 W for both sites combined. Each 429-second session delivers approximately 21.5 J/cm² per site, approximately 0.26 kJ per site, and approximately 0.51 kJ for both sites combined. Over 18 sessions (3 times weekly for 6 weeks), cumulative exposure is approximately 386 J/cm² per site, approximately 4.6 kJ per site, and approximately 9.3 kJ for both sites combined. |
| Arm C - Experimental: Pulsed Wave (PW) | Experimental | Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)Participants receive bilateral 808-nm tPBM in pulsed mode over AF3/F3 and AF4/F4, using the same two round beams of approximately 12 cm² each (approximately 24 cm² total) and the same 429-second session duration as the other active arms. Light is pulsed at 42 Hz with a 33% duty cycle (pulse period approximately ~24 ms; approximately ~8 ms ON and approximately 16 ms OFF; approximately 18,000 pulses per session). Peak irradiance is approximately 900 mW/cm², corresponding to approximately 10.8 W peak optical power per site and approximately 21.6 W peak for both sites combined. Time-averaged irradiance is approximately 300 mW/cm², corresponding to approximately 3.6 W average per site and approximately 7.2 W average for both sites combined, matched to Arm A. Delivered energy is therefore identical to Arm A. This arm isolates waveform (pulsed vs continuous) at matched average irradiance and matched total delivered energy. |
| Arm D - Sham Comparator: Sham tPBM | Sham comparator | Device: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)Participants undergo identical procedures with an identical-appearing device positioned over AF3/F3 and AF4/F4 that emits no therapeutic near-infrared light (0 mW/cm², 0 W, and 0 J at each site and for both sites combined). Session duration (429 seconds), frequency (3 times weekly for 6 weeks, 18 sessions), device setup, operator contact, and all visible and audible device cues are matched to the active arms to maintain blinding. Because 808-nm light is invisible, no perceptual cue distinguishes active from sham emission. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (11 listed)
- A decrease in self-reported SDQ from screening to baseline ≥30%, calculated as [((SDQscreening-88) - (SDQbaseline-88)) / (SDQscreening-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).
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 |
|---|---|---|
| Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM)Also: NIR-TLT808-nm near-infrared laser light is delivered through a headset forming approximately uniform, round beams of approximately 12 cm² at each of 2 bilateral frontal scalp sites (EEG positions AF3/F3 and AF4/F4; approximately 24 cm² total), irradiated simultaneously. Arms: (1) CW, Medium Dose, approximately 300 mW/cm² average irradiance (3.6 W per site; 7.2 W both sites); (2) CW_LOW, approximately 50 mW/cm² (0.6 W per site; 1.2 W both sites); (3) PW, 42 Hz, 33% duty cycle, peak approximately 900 mW/cm² (10.8 W per site; 21.6 W both sites), average approximately 300 mW/cm² (3.6 W per site; 7.2 W both sites); (4) Sham, identical device and procedural cues, no therapeutic emission (0 mW/cm²). Sessions lasted 429 seconds, 3 times weekly for 6 weeks (18 sessions). Sham duration and procedures matched the active arms to maintain blinding. | Device | Arm A - Experimental: Continuous Wave (CW, Medium Dose), Arm B - Experimental: Continuous Wave Low Dose (CW_LOW), Arm C - Experimental: Pulsed Wave (PW), Arm D - Sham Comparator: Sham tPBM |
Primary outcome
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).
1 secondary outcome
Secondary Outcome Measures
Time frame: QIDS-C 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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Background: PubMed 19233936Zivin JA, Albers GW, Bornstein N, Chippendale T, Dahlof B, Devlin T, Fisher M, Hacke W, Holt W, Ilic S, Kasner S, Lew R, Nash M, Perez J, Rymer M, Schellinger P, Schneider D, Schwab S, Veltkamp R, Walker M, Streeter J; NeuroThera Effectiveness and Safety Trial-2 Investigators. Effectiveness and safety of transcranial laser therapy for acute ischemic stroke. Stroke. 2009 Apr;40(4):1359-64. doi: 10.1161/STROKEAHA.109.547547. Epub 2009 Feb 20.
- Background: PubMed 10938785Zhang Q, Ma H, Nioka S, Chance B. Study of near infrared technology for intracranial hematoma detection. J Biomed Opt. 2000 Apr;5(2):206-13. doi: 10.1117/1.429988.
- Background: PubMed 9421973Yu W, Naim JO, McGowan M, Ippolito K, Lanzafame RJ. Photomodulation of oxidative metabolism and electron chain enzymes in rat liver mitochondria. Photochem Photobiol. 1997 Dec;66(6):866-71. doi: 10.1111/j.1751-1097.1997.tb03239.x.
- Background: PubMed 19347944Yamaura M, Yao M, Yaroslavsky I, Cohen R, Smotrich M, Kochevar IE. Low level light effects on inflammatory cytokine production by rheumatoid arthritis synoviocytes. Lasers Surg Med. 2009 Apr;41(4):282-90. doi: 10.1002/lsm.20766.
- Background: PubMed 27379735Xu Z, Guo X, Yang Y, Tucker D, Lu Y, Xin N, Zhang G, Yang L, Li J, Du X, Zhang Q, Xu X. Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mice. Mol Neurobiol. 2017 Aug;54(6):4551-4559. doi: 10.1007/s12035-016-9983-2. Epub 2016 Jul 5.
- Background: PubMed 22334326Wu X, Alberico SL, Moges H, De Taboada L, Tedford CE, Anders JJ. Pulsed light irradiation improves behavioral outcome in a rat model of chronic mild stress. Lasers Surg Med. 2012 Mar;44(3):227-32. doi: 10.1002/lsm.22004. Epub 2012 Feb 14.
- BackgroundThomson, D. J. (1982). Spectrum estimation and harmonic analysis. Proceedings of the IEEE, 70(9), 1055-1096.
- Background: PubMed 17681762Simon NM, McNamara K, Chow CW, Maser RS, Papakostas GI, Pollack MH, Nierenberg AA, Fava M, Wong KK. A detailed examination of cytokine abnormalities in Major Depressive Disorder. Eur Neuropsychopharmacol. 2008 Mar;18(3):230-3. doi: 10.1016/j.euroneuro.2007.06.004. Epub 2007 Aug 3.
- Background: PubMed 19995444Schiffer F, Johnston AL, Ravichandran C, Polcari A, Teicher MH, Webb RH, Hamblin MR. Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety. Behav Brain Funct. 2009 Dec 8;5:46. doi: 10.1186/1744-9081-5-46.
- Background: PubMed 20479761Shelton RC, Claiborne J, Sidoryk-Wegrzynowicz M, Reddy R, Aschner M, Lewis DA, Mirnics K. Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Mol Psychiatry. 2011 Jul;16(7):751-62. doi: 10.1038/mp.2010.52. Epub 2010 May 18.
- Background: PubMed 9881538Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.
- Background: PubMed 27367569Salehpour F, Rasta SH, Mohaddes G, Sadigh-Eteghad S, Salarirad S. Therapeutic effects of 10-HzPulsed wave lasers in rat depression model: A comparison between near-infrared and red wavelengths. Lasers Surg Med. 2016 Sep;48(7):695-705. doi: 10.1002/lsm.22542. Epub 2016 Jul 1.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) in people with Depression and Depressive Disorder, run by NeuroThera DE at 2 sites in Peru.
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 3 inclusion and 11 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: finished, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Peru. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect on depressive symptoms (time frame: Baseline, mid-treatment (Week 3), post-treatment (Week 6), and at 2-week follow-up (Week 8).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06934135, which also lists 60 linked publications.
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 24 Sep 2026.