Near-infrared Transcranial Laser Therapy in Subjects With Major Depressive Disorder: A Study of Dosing With Laser.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- Effect on depressive symptoms
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, care providers, investigators, outcome assessors (those evaluating the results), and the sponsor are blinded to the group assignments.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •A decrease in self-reported SDQ from screening to baseline ≥30%, calculated as [((SDQ_screening-88) - (SDQ_baseline-88)) / (SDQ_screening-88)] ≥30/
- •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.
研究组 & 干预措施
Arm B - Experimental: Continuous Wave Low Dose (CW_LOW)
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.
干预措施: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) (Device)
Arm C - Experimental: Pulsed Wave (PW)
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.
干预措施: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) (Device)
Arm D - Sham Comparator: Sham 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.
干预措施: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) (Device)
Arm A - Experimental: Continuous Wave (CW, Medium Dose)
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.
干预措施: Bilateral Near-Infrared Transcranial Photobiomodulation (tPBM) (Device)
结局指标
主要结局
Effect on depressive symptoms
时间窗: 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).
次要结局
- Secondary Outcome Measures(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).)
- 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).)