Major Depressive DisorderNCT04619121
Near-infrared Radiation-transcranial Photobiomodulation for Major Depressive Disorder
A study testing NIR-tPBM in people with Major Depressive Disorder and Oxidative Stress, run by China Medical University Hospital at 1 site in Taiwan.
Trial summary
This study was designed to be a 3 year, 3 phases project, and will explore the therapeutic effects from near-infrared transcranial photobiomodulation (NIR tPBM) in major depressive disordered human subjects, and it's biological mechanisms in cellular and animal model. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Major Depressive Disorder, Oxidative Stress
- What is being tested?
- NIR-tPBM
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteTaiwan
- Study dates
- 21 Dec 2020to 31 Jul 2022
- 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
- Subjects may be included in the study only if they meet all of the following criteria:
- The subject should be between at least 18 years of age at screening, but has not had their 76th birthday at screening.
- Diagnosis of major depressive disorder (Based on Diagnostic Statistical Manual-IV or 5 ; diagnosis code: 296.22-296.23、296.32-296.33).
- HAM-D-17 ≥14 and ≤ 25
- Subject Informed Consent obtained in writing in compliance with local regulations prior to enrollment into this study.
- The subject (and caregiver, if applicable) is willing to participate in this study for at least 12 weeks.
- Subjects may only be taking one (1) antidepressant, and will need to be on a stable dose for at least four weeks prior to enrollment.
Who cannot join
- Subjects will be excluded from the study for any of the following reasons:
- The subject is pregnant or lactating.
- The subject failed two or more FDA-approved antidepressants during current episode.
- Structured psychotherapy focused on treating the subject's depression is exclusionary unless the subject has had at least 8 weeks of treatment prior to the screening visit.
- Substance used disorder in the past 6 months.
- Psychotic disorder or psychotic episode (current psychotic episode per assessment).
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- Bipolar affective disorder (per assessment).
- Unstable or active medical illness.
- Active suicidal or homicidal ideation.
- The subject has a significant skin condition (i.e., hemangioma, scleroderma, psoriasis, rash, open wound or tattoo) on the subject's scalp that is found to be directly below any of the procedure sites.
- The subject has an implant of any kind in the head (e.g. stent, clipped aneurysm, embolized AVM, implantable shunt - Hakim valve).
- Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
China Medical University Beigang Hospital
Beigang, Yunlin County, 651012
About this study
Official title: Near-infrared Radiation-transcranial Photobiomodulation for Major Depressive Disorder: From Cellular, Animal Studies to a Sham-controlled Double-blind Randomized Clinical Trial
This study was designed to be a 3 year, 3 phases project, and will explore the therapeutic effects from near-infrared transcranial photobiomodulation (NIR tPBM) in major depressive disordered human subjects, and it's biological mechanisms in cellular and animal model. However, due to shortage of funding under the pandemics, the project is now modified to start from its clinical part first, and will continue to its basic parts later when funding resources in place.
Read the detailed description
Major depressive disorder (MDD) is a leading cause of the overall global burden of disease in modern society, and has been estimated to move into the first place by 2030. Current antidepressants and psychotherapy had proved their efficacy, but are limited by the adverse effects and shortage of capable therapists worldwide. Accumulating evidence showed that hypometabolism of global and specific brain regions, inflammation, oxidative stress, suppression of neurogenesis and disturbed circadian rhythm all contribute to the pathophysiology of MDD.
Dr. Paolo Cassano, MD, PhD and his team from the Massachusetts General Hospital (MGH) of Harvard University recently demonstrated in both animal and human subjects that near-infrared radiation-transcranial photobiomodulation (NIR-tPBM) is a well-tolerated and effective treatment modality for MDD, and hypothesized NIR-tPBM may activate brain metabolism, be anti-inflammatory, reduce oxidative stress and promote neurogenesis. So far, the clinical studies are either open-labeled or only of small scale (n=21), and the real antidepressant mechanism of NIR-tPBM has not yet been fully understood. Adequately powered, well designed, double-blind randomized-control trials of larger scale is in pressing need.
In this 3-year study, we will collaborate with the team from Harvard University and MGH, to comprehensively evaluate from cellular mechanism, animal model, to clinical trials in human, the underlying mechanism of NIR-tPBM and the clinical strategy of NIR-tPBM. In the cellular study, we will culture and treat the human neuron-like cell lines with continuous NIR-PBM of different dosimetry and different duration, and compare the differences in cellular circadian rhythm, energy metabolism, and inflammation markers as well as the underlying gene expression. In the animal study, the mice under chronic stress environment will be treated with NIR-tPBM of different duration. We will compare the behavioral differences relevant to anxiety, depression and cognitive performance, as well as the differences in neurogenesis, neuroplasticity, energy metabolism, circadian rhythm, and inflammation markers of the mice and the gene expression of the biomarkers. In both cellular and animal studies, dose-response assessment will be applied. In the clinical human study, we will conduct a prospective, double-blind, randomized, sham-controlled trial, recruiting totally 80 MDD patients, age 18 to 75, and apply adjunctive NIR t-PBM to the dorsolateral prefrontal cortex, bilaterally and simultaneously, from 20 minutes and up to 80 minutes a day under the evaluation and recommendation of the clinicians, for 8 consecutive weeks. The change in depressive symptoms and circadian behaviors will be recorded in the 0, 2, 4, 8, 12 weeks and compared. The patient's peripheral blood-based biochemistry profile, inflammatory, oxidative stress, and circadian rhythm markers, as well as the gene expression of the relevant markers, will be collected in week 0, 8, and 12, and be compared.
- Conditions
- Major Depressive Disorder, Oxidative Stress
- Being tested
- NIR-tPBM, Sham device
- Keywords
- near-infrared radiation-transcranial photobiomodulation, circadian rhythm, Inflammation, Brain energy metabolism
- Medical subject headings
- Depressive Disorder, Major, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NIR-tPBMDevice
Also called near-infrared transcranial photobiomodulation
The treatment will last for 8 weeks and be bilateral and applied to the frontal areas with one application site on the left side and one on the right side (left and right forehead centered on the frontal eminences and per EEG sites on F3 and F4). Energy is administered with a radiation wavelength of 830 nm. The duration of irradiation is from 20 minutes at each application site (the 2 sites are irradiated at the same time which is equivalent to 20 minutes of total time) to 40 minutes at each site, up to 2 times per day. The treatment will follow these specifications: PBM (IR) irradiance of 33.2 mW/cm2, each treatment window area is 28.7 cm2; PBM (IR) fluence of up to 60 Joules/cm2; energy delivered per session per device up to 1.72 kJ for a total of up to 3.44 kJ.
Sham deviceDevice
Also called Sham
The sham device is completely identical in appearance, but only emits neglectable energy to the brain.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with real NIR-tPBM on top of standing pharmacotherapy | Experimental | NIR t-PBM to the dorsolateral prefrontal cortex, bilaterally and simultaneously, from 20 minutes to 80 minutes a day, for 8 consecutive weeks. Receives: Device: NIR-tPBM |
| Sham device on top of standing pharmacotherapy | Sham comparator | Sham device with neglectable energy to the dorsolateral prefrontal cortex, bilaterally and simultaneously, from 20 minutes to 80 minutes a day, for 8 consecutive weeks. Receives: Device: Sham device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in depressive symptoms (subjective)
Measured with Beck Depression Rating scale, value from 0 to 63, with higher scores indicating greater severity of depression.
Measured: Measured biweekly up to 12 weeks.
Change in depressive symptoms (objective)
Measured with Hamilton Depression rating scale (21-items), value from 0 to 66, with higher scores indicating greater severity of depression.
Measured: Measured biweekly until trial completed, up to 12 weeks.
Secondary outcomes (2)
Change in circadian rhythm
Measured with Munich ChronoType Questionnaire (MCTQ), value of 16 to 86. It offers methods to make up for sleep log, and measures the behavioral change around the clock.
Measured: Measured biweekly up to 12 weeks.
Change in sleep quality
Measured with Pittsburgh Sleep Quality Index,value of 0 to 21, provides a subjective measure of sleep quality and patterns. The higher the score, the worse the quality.
Measured: Measured twice a week up to 12 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2020
- Study start21 Dec 2020
- Primary completion31 May 2022
- Study completion31 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by China Medical University HospitalThe sponsor's other registered studies.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- China Medical University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Responsible party
- Principal investigator, Ta-wei Guu, China Medical University Hospital
- Investigators
- Ta-Wei Guu, MD, Principal investigator, China Medical University, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04619121
- Sponsor's protocol ID
- CMUH109-REC3-054
- Status last verified
- Dec 2022
- First submitted
- 26 Oct 2020
- Last updated
- 4 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Will be discussed internally after trial completed.
Publications
Caldieraro MA, Cassano P. Transcranial and systemic photobiomodulation for major depressive disorder: A systematic review of efficacy, tolerability and biological mechanisms. J Affect Disord. 2019 Jan 15;243:262-273. doi: 10.1016/j.jad.2018.09.048. Epub 2018 Sep 17.
PubMed 30248638Salehpour F, Cassano P, Rouhi N, Hamblin MR, De Taboada L, Farajdokht F, Mahmoudi J. Penetration Profiles of Visible and Near-Infrared Lasers and Light-Emitting Diode Light Through the Head Tissues in Animal and Human Species: A Review of Literature. Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):581-595. doi: 10.1089/photob.2019.4676. Epub 2019 Sep 25.
PubMed 31553265Cassano P, Caldieraro MA, Norton R, Mischoulon D, Trinh NH, Nyer M, Dording C, Hamblin MR, Campbell B, Iosifescu DV. Reported Side Effects, Weight and Blood Pressure, After Repeated Sessions of Transcranial Photobiomodulation. Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):651-656. doi: 10.1089/photob.2019.4678.
PubMed 31647774Cassano P. Photomedicine and Pharmaceuticals: A Brain New Deal. Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):575-576. doi: 10.1089/photob.2019.4733. Epub 2019 Sep 24. No abstract available.
PubMed 31549918Guu TW, Cassano P, Li WJ, Tseng YH, Ho WY, Lin YT, Lin SY, Chang JP, Mischoulon D, Su KP. Wearable, self-administered transcranial photobiomodulation for major depressive disorder and sleep: A randomized, double blind, sham-controlled trial. J Affect Disord. 2025 Mar 1;372:635-642. doi: 10.1016/j.jad.2024.12.065. Epub 2024 Dec 18.
PubMed 39706483
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Near-infrared Radiation-transcranial Photobiomodulation for Major Depressive Disorder: From Cellular, Animal Studies to a Sham-controlled Double-blind Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04619121
- Acronym / sponsor ID
- CMUH109-REC3-054
- Conditions
- Major Depressive Disorder, Oxidative Stress
- Keywords
- near-infrared radiation-transcranial photobiomodulation, circadian rhythm, Inflammation, Brain energy metabolism
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- China Medical University HospitalUniversity, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Study start
- 21 Dec 2020 (actual)
- Primary completion
- 31 May 2022 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 6 Nov 2020 (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.
This study was designed to be a 3 year, 3 phases project, and will explore the therapeutic effects from near-infrared transcranial photobiomodulation (NIR tPBM) in major depressive disordered human subjects, and it's biological mechanisms in cellular and animal model. However, due to shortage of funding under the pandemics, the project is now modified to start from its clinical part first, and will continue to its basic parts later when funding resources in place.
Detailed description
Major depressive disorder (MDD) is a leading cause of the overall global burden of disease in modern society, and has been estimated to move into the first place by 2030. Current antidepressants and psychotherapy had proved their efficacy, but are limited by the adverse effects and shortage of capable therapists worldwide. Accumulating evidence showed that hypometabolism of global and specific brain regions, inflammation, oxidative stress, suppression of neurogenesis and disturbed circadian rhythm all contribute to the pathophysiology of MDD.
Dr. Paolo Cassano, MD, PhD and his team from the Massachusetts General Hospital (MGH) of Harvard University recently demonstrated in both animal and human subjects that near-infrared radiation-transcranial photobiomodulation (NIR-tPBM) is a well-tolerated and effective treatment modality for MDD, and hypothesized NIR-tPBM may activate brain metabolism, be anti-inflammatory, reduce oxidative stress and promote neurogenesis. So far, the clinical studies are either open-labeled or only of small scale (n=21), and the real antidepressant mechanism of NIR-tPBM has not yet been fully understood. Adequately powered, well designed, double-blind randomized-control trials of larger scale is in pressing need.
In this 3-year study, we will collaborate with the team from Harvard University and MGH, to comprehensively evaluate from cellular mechanism, animal model, to clinical trials in human, the underlying mechanism of NIR-tPBM and the clinical strategy of NIR-tPBM. In the cellular study, we will culture and treat the human neuron-like cell lines with continuous NIR-PBM of different dosimetry and different duration, and compare the differences in cellular circadian rhythm, energy metabolism, and inflammation markers as well as the underlying gene expression. In the animal study, the mice under chronic stress environment will be treated with NIR-tPBM of different duration. We will compare the behavioral differences relevant to anxiety, depression and cognitive performance, as well as the differences in neurogenesis, neuroplasticity, energy metabolism, circadian rhythm, and inflammation markers of the mice and the gene expression of the biomarkers. In both cellular and animal studies, dose-response assessment will be applied. In the clinical human study, we will conduct a prospective, double-blind, randomized, sham-controlled trial, recruiting totally 80 MDD patients, age 18 to 75, and apply adjunctive NIR t-PBM to the dorsolateral prefrontal cortex, bilaterally and simultaneously, from 20 minutes and up to 80 minutes a day under the evaluation and recommendation of the clinicians, for 8 consecutive weeks. The change in depressive symptoms and circadian behaviors will be recorded in the 0, 2, 4, 8, 12 weeks and compared. The patient's peripheral blood-based biochemistry profile, inflammatory, oxidative stress, and circadian rhythm markers, as well as the gene expression of the relevant markers, will be collected in week 0, 8, and 12, and be compared.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment with real NIR-tPBM on top of standing pharmacotherapy | Experimental | Device: NIR-tPBMNIR t-PBM to the dorsolateral prefrontal cortex, bilaterally and simultaneously, from 20 minutes to 80 minutes a day, for 8 consecutive weeks. |
| Sham device on top of standing pharmacotherapy | Sham comparator | Device: Sham deviceSham device with neglectable energy to the dorsolateral prefrontal cortex, bilaterally and simultaneously, from 20 minutes to 80 minutes a day, for 8 consecutive weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects may be included in the study only if they meet all of the following criteria:
Key exclusion criteria (12 listed)
- Subjects will be excluded from the study for any of the following reasons:
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 |
|---|---|---|
| NIR-tPBMAlso: near-infrared transcranial photobiomodulationThe treatment will last for 8 weeks and be bilateral and applied to the frontal areas with one application site on the left side and one on the right side (left and right forehead centered on the frontal eminences and per EEG sites on F3 and F4). Energy is administered with a radiation wavelength of 830 nm. The duration of irradiation is from 20 minutes at each application site (the 2 sites are irradiated at the same time which is equivalent to 20 minutes of total time) to 40 minutes at each site, up to 2 times per day. The treatment will follow these specifications: PBM (IR) irradiance of 33.2 mW/cm2, each treatment window area is 28.7 cm2; PBM (IR) fluence of up to 60 Joules/cm2; energy delivered per session per device up to 1.72 kJ for a total of up to 3.44 kJ. | Device | Treatment with real NIR-tPBM on top of standing pharmacotherapy |
| Sham deviceAlso: ShamThe sham device is completely identical in appearance, but only emits neglectable energy to the brain. | Device | Sham device on top of standing pharmacotherapy |
Primary outcome
Change in depressive symptoms (subjective)
Time frame: Measured biweekly up to 12 weeks.
Measured with Beck Depression Rating scale, value from 0 to 63, with higher scores indicating greater severity of depression.
Change in depressive symptoms (objective)
Time frame: Measured biweekly until trial completed, up to 12 weeks.
Measured with Hamilton Depression rating scale (21-items), value from 0 to 66, with higher scores indicating greater severity of depression.
2 secondary outcomes
Change in circadian rhythm
Time frame: Measured biweekly up to 12 weeks.
Change in sleep quality
Time frame: Measured twice a week up to 12 weeks.
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 4 Jan 2023.
- Background: PubMed 30248638Caldieraro MA, Cassano P. Transcranial and systemic photobiomodulation for major depressive disorder: A systematic review of efficacy, tolerability and biological mechanisms. J Affect Disord. 2019 Jan 15;243:262-273. doi: 10.1016/j.jad.2018.09.048. Epub 2018 Sep 17.
- Background: PubMed 31553265Salehpour F, Cassano P, Rouhi N, Hamblin MR, De Taboada L, Farajdokht F, Mahmoudi J. Penetration Profiles of Visible and Near-Infrared Lasers and Light-Emitting Diode Light Through the Head Tissues in Animal and Human Species: A Review of Literature. Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):581-595. doi: 10.1089/photob.2019.4676. Epub 2019 Sep 25.
- Background: PubMed 31647774Cassano P, Caldieraro MA, Norton R, Mischoulon D, Trinh NH, Nyer M, Dording C, Hamblin MR, Campbell B, Iosifescu DV. Reported Side Effects, Weight and Blood Pressure, After Repeated Sessions of Transcranial Photobiomodulation. Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):651-656. doi: 10.1089/photob.2019.4678.
- Background: PubMed 31549918Cassano P. Photomedicine and Pharmaceuticals: A Brain New Deal. Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):575-576. doi: 10.1089/photob.2019.4733. Epub 2019 Sep 24. No abstract available.
- Derived from this study: PubMed 39706483Guu TW, Cassano P, Li WJ, Tseng YH, Ho WY, Lin YT, Lin SY, Chang JP, Mischoulon D, Su KP. Wearable, self-administered transcranial photobiomodulation for major depressive disorder and sleep: A randomized, double blind, sham-controlled trial. J Affect Disord. 2025 Mar 1;372:635-642. doi: 10.1016/j.jad.2024.12.065. Epub 2024 Dec 18.
- Individual participant dataSharing planned: Undecided. Will be discussed internally after trial completed.
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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.
Ta-Wei Guu, MD principal investigator
China Medical University, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NIR-tPBM in people with Major Depressive Disorder and Oxidative Stress, run by China Medical University Hospital at 1 site in Taiwan.
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 7 inclusion and 12 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 4 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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?
Change in depressive symptoms (subjective) (time frame: Measured biweekly up to 12 weeks.). The study lists 2 primary outcomes in all. 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 NCT04619121, which also lists 5 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 4 Jan 2023.