Autism Spectrum DisorderNCT05363982
Evaluation of Transcranial Photobiomodulation in Autism Spectrum Disorder
A study testing Transcranial Photobiomodulation (tPBM) in people with Autism Spectrum Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The purpose of this 8-week double-blind randomized placebo-controlled study is to assess the tolerability, safety, and efficacy of tPBM in adult patients with ASD. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- Transcranial Photobiomodulation (tPBM)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Feb 2022to 31 Oct 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female participants between 18 and 59 years of age (inclusive)
- Fulfills Diagnostic and Statistical Manual-5th edition diagnostic criteria for autism spectrum disorder as established by the clinical diagnostic interview.
- Participants with at least moderately severity of ASD symptoms as demonstrated by SRS raw score ≥ 85 and CGI-ASD severity score ≥ 4
- Participants must understand the nature of the study. Participants must be deemed not to have impaired decision-making capacity and must have the capacity to provide direct informed consent. Participants must sign an Institutional Review Board-approved informed consent form before initiation of any study procedures.
- Participants must have a level of understanding sufficient to communicate with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol.
- Participant experiencing a major psychiatric disorder will be allowed to participate in the study provided they do not meet any exclusionary criteria.
- Women of child-bearing potential must use a double-barrier method for birth control (e.g. condoms with spermicide) if sexually active.
- The subject is willing to participate in this study.
Who cannot join
- Impaired intellectual capacity (clinically determined). Participants' intellectual capacity will be assessed during the clinical evaluation and determination will be based on intact communicative language, ability to take personal care, history of holding a job and completion of high school (or equivalency credential), and no history of intellectual disability.
- Participant is unable to communicate due to delay in, or total lack of, spoken language development (grossly impaired language skills)
- Clinically unstable psychiatric conditions or judged to be at serious safety risk to self (suicidal risk) or others (within past 30 days).
- Subjects currently (within past 30 days) experiencing significant symptoms of major psychiatric disorders as clinically determined.
- Subjects with an unstable medical condition (that requires clinical attention).
- Active suicidal or homicidal ideation, as determined by clinical screening.
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- The subject has a significant skin condition at the procedure sites (i.e., hemangioma, scleroderma, psoriasis, rash, open wound or tattoo).
- The subject has an implant of any kind in the head (e.g. stent, clipped aneurysm, embolised arteriovenous malformation, implantable shunt - Hakim valve).
- Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment (verteporfin - for age related macular degeneration; Aminolevulinic Acid- for actinic keratoses; 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)
- Current treatment with a psychotropic medication on a dose that has not been stable for at least 4 weeks prior to initiating study treatment.
- Investigator and his/her immediate family, defined as the investigator's spouse, parent, child, grandparent, or grandchild.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Evaluation of Transcranial Photobiomodulation in Autism Spectrum Disorder: Double-Blind, Placebo-Controlled, Randomized Clinical Study of a Novel Approach
The purpose of this 8-week double-blind randomized placebo-controlled study is to assess the tolerability, safety, and efficacy of tPBM in adult patients with ASD.
Read the detailed description
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by variable presentation of difficulties with socialization, reciprocal communication, and restrictive/repetitive behaviors. An increasingly higher prevalence of ASD is documented in each successive epidemiological survey and the disorder is now estimated to affect up to 2% of youth in the general population. This rise in prevalence is in part attributed to improved recognition of autism in intellectually capable populations.
Currently, there exists no approved treatments for core features of ASD. Instead, available treatment interventions target other psychiatric disorders that frequently co-occur with ASD, including attention, anxiety, and mood disorders.
Transcranial Photobiomodulation (tPBM) is a novel treatment approach based on application of an invisible, non-ionizing electromagnetic wave that results in metabolic modulation in tissues targeted. This intervention consists of exposing bilaterally the frontal brain to the electromagnetic wave that penetrates the skin and skull into brain tissue, is non-invasive and minimally dissipated as thermal energy. The benefits of tPBM are wavelength specific. Electromagnetic wave at 850nm is absorbed by cytochrome c oxidase, a specific chromophore in mitochondria and is associated with increased adenosine triphosphate (ATP) production through the respiratory chain. Ultimately, the increased ATP production leads to increased energy metabolism and activity for the cell, and it is hypothesized that a signaling cascade is also activated promoting cellular plasticity and cytoprotection.
These properties of the tPBM have led to novel therapeutic applications in neurology. In acute ischemic stroke subjects, acute treatment with the tPBM led to significantly better outcome as compared to sham. These results were confirmed in a different cohort of stroke patients with mild to moderate severity of illness. Both studies on stroke subjects showed no significant difference in rate of adverse events, as well as serious adverse events, between the tPBM and sham treated subjects. The tPBM has also been used as a treatment of alopecia and in animal models for methanol-induced retinal toxicity. The tPBM is already widely used for non-invasive assessment of brain function, replacing functional magnetic resonance imaging (fMRI), in studies of infants and young adults, under the name of Near Infrared Spectroscopy) underscoring the relatively low risk of tPBM. The major risk of tPBM when using a laser as the light source is associated with accidental retinal exposure, when beams are projected through the lens, with increased risk of macular degeneration. Light emitting diode (LED) light does not share the same risk level as laser light sources and this clinical trial will have multiple protections to safeguard against this risk.
Proposed treatment with tPBM has been previously studied in patients with Major Depressive Disorder (MDD). MDD has been associated with deficits in brain bioenergetic metabolism. In an experimental model of depression, the mitochondrial respiratory chain was found to be inhibited by chronic stress. Depressed subjects have also significantly lower production of ATP (an energy vector) in their muscle tissue and greater incidence of deletions in their mitochondrial DNA. Data from magnetic resonance spectroscopy in subjects with MDD showed that response to the augmentation of a selective serotonin reuptake inhibitor (SSRI) with triiodothyronine (a thyroid hormone) is associated with restoration of the levels of ATP in the brain. A preliminary open study in 10 depressed subjects has shown that the tPBM was safe, effective and well tolerated. More recently, efficacy and safety of tPBM was also explored in treatment of ASD with promising results and no serious adverse events. In that study, 40 participants received eight 5-min laser light applications to the base of the skull and temporal areas across 4-week period (2 applications per week). A pulsed laser of 635nm was compared to placebo (very weak LEDs) and was shown to be associated with significant improvement in ASD symptoms. Tissue penetration varies at different wavelengths, with 800-850nm range penetrating into deep tissue compared to that of 635nm.
More recently, the investigators completed a prospective, 8-week open-label treatment trial of tPBM in 10 adult patients with moderate to severe level of ASD. Short-term tPBM was well tolerated and was effective in reducing symptom severity of ASD and comorbid ADHD. In addition, tPBM treatment was associated with improvements in executive functions, specifically in functional domains of cognitive flexibility and emotional control, planning and organization, response inhibition and significant improvement in overall function. Treatment with tPBM was well tolerated, and there were no serious adverse events. One subject experienced headache 8 hours after first treatment, and another patient had insomnia after the first treatment episode. Both patients recovered spontaneously and required no changes to study treatments. Current project involves a double-blind randomized clinical trial of tPBM in adult patients with ASD.
The main aim of this 8-week, prospective, placebo (sham) controlled study is to evaluate the efficacy, safety, and tolerability of tPBM with near-infrared light in intellectually capable adults with ASD. Because the tPBM is a non-ionizing radiation, multiple sessions are expected to be safe.
The tPBM treatment can be completed in the comfort of participants' homes, while monitoring their safety and response during scheduled visits. This clinical trial will answer whether tPBM has an effect on ASD symptoms and whether it is safe and acceptable among patients with ASD, for whom frequent visits otherwise would be prohibitive or render it inaccessible.
The advantage of the tPBM treatment approach as compared to pharmacotherapy is that adherence can be easily monitored with device recordings, and the patient is not required to ingest any substance. This proposed study will contribute to answer the question of whether tPBM has an effect on ASD symptoms and whether it is acceptable in minority populations, thus justifying further studies and investments.
- Conditions
- Autism Spectrum Disorder
- Being tested
- Transcranial Photobiomodulation (tPBM), Placebo/ Sham
- Keywords
- Autism, Transcranial Photobiomodulation
- Medical subject headings
- Autism Spectrum Disorder, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Photobiomodulation (tPBM)Device
Transcranial Photobiomodulation (tPBM) is a novel treatment approach based on application of an invisible, non-ionizing electromagnetic wave that results in metabolic modulation in tissues targeted. This intervention consists of exposing bilaterally the frontal brain to the electromagnetic wave that penetrates the skin and skull into brain tissue, is non-invasive and minimally dissipated as thermal energy.
Other Names:
Niraxx G1 Headband
Placebo/ ShamDevice
The sham treatment will consist of applying all the procedures for the delivery of tPBM, but will not deliver light.
| Study group | Role | What they receive |
|---|---|---|
| Transcranial Photobiomodulation (tPBM) Treatment | Active comparator | Transcranial Photobiomodulation--a noninvasive intervention in which near-infrared light is applied to forebrain. Receives: Device: Transcranial Photobiomodulation (tPBM) |
| Placebo/ Sham Treatment | Sham comparator | The sham treatment will mimic the tPBM procedure, while delivering no light. Receives: Device: Placebo/ Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participant Improvement in ASD Symptoms as Assessed by the Clinical Global Impression of Improvement for Autism Spectrum Disorder (CGI-ASD-I)
The CGI-ASD-I is a clinician-rated measure of ASD symptom improvement since baseline. Improvement scores range from 1 (very much improved) to 7 (very much worse). The outcome reported reflects the number of participants who had CGI-ASD-I scores of 1 or 2 at study endpoint.
Measured: Week 8
Treatment Responders
Treatment responders at study endpoint are defined as those who have a Clinical Global Impression of Improvement for ASD (CGI-ASD-I) score ≤2 and a 25% reduction in score from baseline to study endpoint in the Social Responsiveness Scale-Version 2 (SRS-2) total raw score.
Measured: Week 8
Change From Baseline in Social Responsiveness Scale-2 (SRS-2)
The SRS-2 is a parent-rated scale used to identify the presence and severity of social impairment within the autism spectrum and differentiate it from that which occurs in other disorders. It consists of 65 items that rated on a scale from 1 (not true) to 4 (almost always true). The item scores are recoded by a scorer to 0 (not true) to 3 (almost always true) and combined into a total score which ranges from 0 to 195, where a higher score indicates a worse outcome. The outcome reported reflects the change from baseline in SRS Total raw scores and negative scores represent improvement (i.e., decrease in severity from baseline).
Measured: Baseline to week 8
Secondary outcomes (11)
Change From Baseline in Adult Behavior Checklist (ABCL) Total T-score
The Adult Behavior Checklist (ABCL) is an observer-rated scale that assesses maladaptive behavioral and emotional problems, social competence and substance use in adults. The item scores are combined into a total score raw score and then transformed into T-scores, ranging from <50 to 80, where a higher T-score indicates a worse outcome. T-scores are calculated with a mean of 50 (population mean) and a standard deviation of 10. This total score reflects overall psychopathology. The outcome reported reflects the change from baseline in ABCL T-scores and negative scores represent improvement (i.e., decrease in severity from baseline).
Measured: Baseline to week 8
Change From Baseline in Adult ADHD Investigator Symptom Report Scale (AISRS)
The Adult ADHD Investigator Symptom Report Scale (AISRS) is a clinician-rated scale that assesses ADHD symptoms. It consists of 18 items that are rated on a scale from 0 (not present) to 3 (severe). The item scores are combined into a total score raw score ranging from 0 to 54, where a higher score indicates a worse outcome. The outcome reported reflects the change from baseline in AISRS scores and negative scores represent improvement (i.e., decrease in severity from baseline).
Measured: Baseline to week 8
Change From Baseline in Adult ADHD Self-Report Scale (ASRS)
The Adult ADHD Self-Report Scale (ASRS) is a patient-rated scale that assesses frequency of ADHD symptoms. It consists of 18 items that are rated on a scale from 0 to 4. The item scores are combined into a total score raw score ranging from 0 to 72, where a higher score indicates a worse outcome. The outcome reported reflects the change from baseline in ASRS scores and negative scores represent improvement (i.e., decrease in severity from baseline).
Measured: Baseline to week 8
Change From Baseline in Behavior Rating Inventory of Executive Function-Adult Self Report Version (BRIEF-A) Total T-score
The BRIEF-A is a patient-rated scale that assesses the patient's level of executive function deficits. It consists of 75 items that are rated on a scale from 1 (never) to 3 (often). The item scores are combined into a total score raw score and then transformed into T-scores, ranging from 32 to 91, where a higher T-score indicates a worse outcome. T-scores are calculated with a mean of 50 (population mean) and a standard deviation of 10. This total score is called the Global Executive Composite (GEC) scale and it reflects overall executive functioning. The outcome reported reflects the change from baseline in BRIEF-A Total T-scores and negative scores represent improvement (i.e., decrease in severity from baseline).
Measured: Baseline to week 8
Improvement in ADHD Symptoms as Assessed by the Clinical Global Impression of Improvement for ADHD (CGI-ADHD-I)
The CGI-ADHD-I is a clinician-rated measure of ADHD symptom improvement since baseline. Improvement scores range from 1 (very much improved) to 7 (very much worse). The outcome reported reflects the number of participants who had CGI-ADHD-I scores of 1 or 2 at study endpoint.
Measured: Week 8
Improvement in Anxiety Symptoms as Assessed by the Clinical Global Impression of Improvement for Anxiety (CGI-Anxiety-I)
The CGI-Anxiety-I is a clinician-rated measure of depression symptom improvement since baseline. Improvement scores range from 1 (very much improved) to 7 (very much worse). The outcome reported reflects the number of participants who had CGI-Anxiety-I scores of 1 or 2 at study endpoint.
Measured: Week 8
Improvement in Depression Symptoms as Assessed by the Clinical Global Impression of Improvement for Depression (CGI-Depression-I)
The CGI-Depression-I is a clinician-rated measure of depression symptom improvement since baseline. Improvement scores range from 1 (very much improved) to 7 (very much worse). The outcome reported reflects the number of participants who had CGI-Depression-I scores of 1 or 2 at study endpoint.
Measured: Week 8
Change From Baseline in Hamilton Anxiety Scale (HAM-A)
The Hamilton Anxiety Scale (HAM-A) is a clinician-rated scale that assesses anxiety. It consists of 14 items that are rated on a scale s absent, mild, moderate, severe, or very severe. The item scores are combined into a total score raw score ranging from 17 to 30, where a higher score indicates a worse outcome The outcome reported reflects the change from baseline in HAM-A scores and negative scores represent improvement (i.e., decrease in severity from baseline).
Measured: Baseline to week 8
Change From Baseline in Hamilton Depression Scale (HAM-D)
The Hamilton Depression Scale (HAM-D) is a clinician-rated scale that assesses severity of depression in adults. It consists of 21 items that are rated on a scale as absent, mild/trivial, moderate or severe. The item scores are combined into a total score raw score ranging from 0 to 50, where a higher score indicates a worse outcome. The outcome reported reflects the change from baseline in HAM-D scores and negative scores represent improvement (i.e., decrease in severity from baseline).
Measured: Baseline to week 8
Change From Baseline in Massachusetts General Hospital Social Emotional Competence Scale (MGH-SEC)
The MGH-SEC is a clinician-rate scale that assesses change in the frequency and severity of core and associated symptoms of ASD. It consists of 37 items that are rated on a scale from 1 (superior) to 8 (severely). The item scores are combined into a total score which ranges from 37 to 296, where a higher score indicates a worse outcome. The outcome reported reflects the change from baseline in MGH-SEC scale scores and negative scores represent improvement (i.e., decrease in severity from baseline).
Measured: Baseline to week 8
Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)
The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is a patient-rated scale that assess evaluate the degree of enjoyment and satisfaction experienced in eight areas of daily functioning. It consists of 16 items that are rated on a scale from 0 (very poor) to 4 (very good). The item scores are combined into a total score raw score ranging from 0 to 64, where a higher score indicates a better quality of life. The outcome reported reflects the change from baseline in Q-LES-Q scores and positive scores represent improvement (i.e., increase in quality of life from baseline).
Measured: Baseline to week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2022
- Study start11 Feb 2022
- Primary completion31 Oct 2024
- Study completion31 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (33)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tolga A Ceranoglu, Massachusetts General Hospital
- Investigators
- T. Atilla Ceranoglu, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05363982
- Sponsor's protocol ID
- 2021- P- 002646
- Status last verified
- Oct 2025
- First submitted
- 27 Apr 2022
- Last updated
- 27 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Achenbach, T. M. and L. A. Rescorla (2003). Manual for ASEBA Adult Forms & Profiles. Burlington, VT, University of Vermont, Research Center for Children, Youth, & Families.
Adler LA, Spencer T, Faraone SV, Kessler RC, Howes MJ, Biederman J, Secnik K. Validity of pilot Adult ADHD Self- Report Scale (ASRS) to Rate Adult ADHD symptoms. Ann Clin Psychiatry. 2006 Jul-Sep;18(3):145-8. doi: 10.1080/10401230600801077.
PubMed 16923651American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA, American Psychiatric Publishing.
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun. 2011 Jan;25(1):40-5. doi: 10.1016/j.bbi.2010.08.003. Epub 2010 Aug 10.
PubMed 20705131Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators and Centers for Disease Control and Prevention (2012).
Blumberg SJ, Bramlett MD, Kogan MD, Schieve LA, Jones JR, Lu MC. Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011-2012. Natl Health Stat Report. 2013 Mar 20;(65):1-11, 1 p following 11.
PubMed 24988818Cassano P, Cusin C, Mischoulon D, Hamblin MR, De Taboada L, Pisoni A, Chang T, Yeung A, Ionescu DF, Petrie SR, Nierenberg AA, Fava M, Iosifescu DV. Near-Infrared Transcranial Radiation for Major Depressive Disorder: Proof of Concept Study. Psychiatry J. 2015;2015:352979. doi: 10.1155/2015/352979. Epub 2015 Aug 19.
PubMed 26356811Cassano P, Petrie SR, Hamblin MR, Henderson TA, Iosifescu DV. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis. Neurophotonics. 2016 Jul;3(3):031404. doi: 10.1117/1.NPh.3.3.031404. Epub 2016 Mar 4.
PubMed 26989758Constantino, J. N. and C. P. Gruber (2012). The Social Responsiveness Scale Manual, Second Edition (SRS-2). Los Angeles, CA, Western Psychological Services.
Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buchmann EV, Kane M, Whelan NT, Whelan HT. Therapeutic photobiomodulation for methanol-induced retinal toxicity. Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3439-44. doi: 10.1073/pnas.0534746100. Epub 2003 Mar 7.
PubMed 12626762Endicott J, Nee J, Harrison W, Blumenthal R. Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol Bull. 1993;29(2):321-6.
PubMed 8290681Endicott, J., R. L. Spitzer, J. L. Fleiss and J. Cohen (1976).
Gardner A, Johansson A, Wibom R, Nennesmo I, von Dobeln U, Hagenfeldt L, Hallstrom T. Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients. J Affect Disord. 2003 Sep;76(1-3):55-68. doi: 10.1016/s0165-0327(02)00067-8.
PubMed 12943934Hamilton, M. (1959).
Hamilton, M. (1960).
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Transcranial Photobiomodulation in Autism Spectrum Disorder: Double-Blind, Placebo-Controlled, Randomized Clinical Study of a Novel Approach
- ClinicalTrials.gov ID
- NCT05363982
- Acronym / sponsor ID
- 2021- P- 002646
- Conditions
- Autism Spectrum Disorder
- Keywords
- Autism, Transcranial Photobiomodulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 11 Feb 2022 (actual)
- Primary completion
- 31 Oct 2024 (actual)
- Study completion
- 31 Oct 2024 (actual)
- First posted
- 6 May 2022 (actual)
- Results
- Posted 27 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this 8-week double-blind randomized placebo-controlled study is to assess the tolerability, safety, and efficacy of tPBM in adult patients with ASD.
Detailed description
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by variable presentation of difficulties with socialization, reciprocal communication, and restrictive/repetitive behaviors. An increasingly higher prevalence of ASD is documented in each successive epidemiological survey and the disorder is now estimated to affect up to 2% of youth in the general population. This rise in prevalence is in part attributed to improved recognition of autism in intellectually capable populations.
Currently, there exists no approved treatments for core features of ASD. Instead, available treatment interventions target other psychiatric disorders that frequently co-occur with ASD, including attention, anxiety, and mood disorders.
Transcranial Photobiomodulation (tPBM) is a novel treatment approach based on application of an invisible, non-ionizing electromagnetic wave that results in metabolic modulation in tissues targeted. This intervention consists of exposing bilaterally the frontal brain to the electromagnetic wave that penetrates the skin and skull into brain tissue, is non-invasive and minimally dissipated as thermal energy. The benefits of tPBM are wavelength specific. Electromagnetic wave at 850nm is absorbed by cytochrome c oxidase, a specific chromophore in mitochondria and is associated with increased adenosine triphosphate (ATP) production through the respiratory chain. Ultimately, the increased ATP production leads to increased energy metabolism and activity for the cell, and it is hypothesized that a signaling cascade is also activated promoting cellular plasticity and cytoprotection.
These properties of the tPBM have led to novel therapeutic applications in neurology. In acute ischemic stroke subjects, acute treatment with the tPBM led to significantly better outcome as compared to sham. These results were confirmed in a different cohort of stroke patients with mild to moderate severity of illness. Both studies on stroke subjects showed no significant difference in rate of adverse events, as well as serious adverse events, between the tPBM and sham treated subjects. The tPBM has also been used as a treatment of alopecia and in animal models for methanol-induced retinal toxicity. The tPBM is already widely used for non-invasive assessment of brain function, replacing functional magnetic resonance imaging (fMRI), in studies of infants and young adults, under the name of Near Infrared Spectroscopy) underscoring the relatively low risk of tPBM. The major risk of tPBM when using a laser as the light source is associated with accidental retinal exposure, when beams are projected through the lens, with increased risk of macular degeneration. Light emitting diode (LED) light does not share the same risk level as laser light sources and this clinical trial will have multiple protections to safeguard against this risk.
Proposed treatment with tPBM has been previously studied in patients with Major Depressive Disorder (MDD). MDD has been associated with deficits in brain bioenergetic metabolism. In an experimental model of depression, the mitochondrial respiratory chain was found to be inhibited by chronic stress. Depressed subjects have also significantly lower production of ATP (an energy vector) in their muscle tissue and greater incidence of deletions in their mitochondrial DNA. Data from magnetic resonance spectroscopy in subjects with MDD showed that response to the augmentation of a selective serotonin reuptake inhibitor (SSRI) with triiodothyronine (a thyroid hormone) is associated with restoration of the levels of ATP in the brain. A preliminary open study in 10 depressed subjects has shown that the tPBM was safe, effective and well tolerated. More recently, efficacy and safety of tPBM was also explored in treatment of ASD with promising results and no serious adverse events. In that study, 40 participants received eight 5-min laser light applications to the base of the skull and temporal areas across 4-week period (2 applications per week). A pulsed laser of 635nm was compared to placebo (very weak LEDs) and was shown to be associated with significant improvement in ASD symptoms. Tissue penetration varies at different wavelengths, with 800-850nm range penetrating into deep tissue compared to that of 635nm.
More recently, the investigators completed a prospective, 8-week open-label treatment trial of tPBM in 10 adult patients with moderate to severe level of ASD. Short-term tPBM was well tolerated and was effective in reducing symptom severity of ASD and comorbid ADHD. In addition, tPBM treatment was associated with improvements in executive functions, specifically in functional domains of cognitive flexibility and emotional control, planning and organization, response inhibition and significant improvement in overall function. Treatment with tPBM was well tolerated, and there were no serious adverse events. One subject experienced headache 8 hours after first treatment, and another patient had insomnia after the first treatment episode. Both patients recovered spontaneously and required no changes to study treatments. Current project involves a double-blind randomized clinical trial of tPBM in adult patients with ASD.
The main aim of this 8-week, prospective, placebo (sham) controlled study is to evaluate the efficacy, safety, and tolerability of tPBM with near-infrared light in intellectually capable adults with ASD. Because the tPBM is a non-ionizing radiation, multiple sessions are expected to be safe.
The tPBM treatment can be completed in the comfort of participants' homes, while monitoring their safety and response during scheduled visits. This clinical trial will answer whether tPBM has an effect on ASD symptoms and whether it is safe and acceptable among patients with ASD, for whom frequent visits otherwise would be prohibitive or render it inaccessible.
The advantage of the tPBM treatment approach as compared to pharmacotherapy is that adherence can be easily monitored with device recordings, and the patient is not required to ingest any substance. This proposed study will contribute to answer the question of whether tPBM has an effect on ASD symptoms and whether it is acceptable in minority populations, thus justifying further studies and investments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transcranial Photobiomodulation (tPBM) Treatment | Active comparator | Device: Transcranial Photobiomodulation (tPBM)Transcranial Photobiomodulation--a noninvasive intervention in which near-infrared light is applied to forebrain. |
| Placebo/ Sham Treatment | Sham comparator | Device: Placebo/ ShamThe sham treatment will mimic the tPBM procedure, while delivering no light. |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male or female participants between 18 and 59 years of age (inclusive)
- Fulfills Diagnostic and Statistical Manual-5th edition diagnostic criteria for autism spectrum disorder as established by the clinical diagnostic interview.
- Participants with at least moderately severity of ASD symptoms as demonstrated by SRS raw score ≥ 85 and CGI-ASD severity score ≥ 4
- Participants must understand the nature of the study. Participants must be deemed not to have impaired decision-making capacity and must have the capacity to provide direct informed consent. Participants must sign an Institutional Review Board-approved informed consent form before initiation of any study procedures.
- Participants must have a level of understanding sufficient to communicate with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol.
Key exclusion criteria (11 listed)
- Impaired intellectual capacity (clinically determined). Participants' intellectual capacity will be assessed during the clinical evaluation and determination will be based on intact communicative language, ability to take personal care, history of holding a job and completion of high school (or equivalency credential), and no history of intellectual disability.
- Participant is unable to communicate due to delay in, or total lack of, spoken language development (grossly impaired language skills)
- Clinically unstable psychiatric conditions or judged to be at serious safety risk to self (suicidal risk) or others (within past 30 days).
- Subjects currently (within past 30 days) experiencing significant symptoms of major psychiatric disorders as clinically determined.
- Subjects with an unstable medical condition (that requires clinical attention).
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 |
|---|---|---|
| Transcranial Photobiomodulation (tPBM)Transcranial Photobiomodulation (tPBM) is a novel treatment approach based on application of an invisible, non-ionizing electromagnetic wave that results in metabolic modulation in tissues targeted. This intervention consists of exposing bilaterally the frontal brain to the electromagnetic wave that penetrates the skin and skull into brain tissue, is non-invasive and minimally dissipated as thermal energy. Other Names: Niraxx G1 Headband | Device | Transcranial Photobiomodulation (tPBM) Treatment |
| Placebo/ ShamThe sham treatment will consist of applying all the procedures for the delivery of tPBM, but will not deliver light. | Device | Placebo/ Sham Treatment |
Primary outcome
Participant Improvement in ASD Symptoms as Assessed by the Clinical Global Impression of Improvement for Autism Spectrum Disorder (CGI-ASD-I)
Time frame: Week 8
The CGI-ASD-I is a clinician-rated measure of ASD symptom improvement since baseline. Improvement scores range from 1 (very much improved) to 7 (very much worse). The outcome reported reflects the number of participants who had CGI-ASD-I scores of 1 or 2 at study endpoint.
Treatment Responders
Time frame: Week 8
Treatment responders at study endpoint are defined as those who have a Clinical Global Impression of Improvement for ASD (CGI-ASD-I) score ≤2 and a 25% reduction in score from baseline to study endpoint in the Social Responsiveness Scale-Version 2 (SRS-2) total raw score.
Change From Baseline in Social Responsiveness Scale-2 (SRS-2)
Time frame: Baseline to week 8
The SRS-2 is a parent-rated scale used to identify the presence and severity of social impairment within the autism spectrum and differentiate it from that which occurs in other disorders. It consists of 65 items that rated on a scale from 1 (not true) to 4 (almost always true). The item scores are recoded by a scorer to 0 (not true) to 3 (almost always true) and combined into a total score which ranges from 0 to 195, where a higher score indicates a worse outcome. The outcome reported reflects the change from baseline in SRS Total raw scores and negative scores represent improvement (i.e., decrease in severity from baseline).
11 secondary outcomes
Change From Baseline in Adult Behavior Checklist (ABCL) Total T-score
Time frame: Baseline to week 8
Change From Baseline in Adult ADHD Investigator Symptom Report Scale (AISRS)
Time frame: Baseline to week 8
Change From Baseline in Adult ADHD Self-Report Scale (ASRS)
Time frame: Baseline to week 8
Change From Baseline in Behavior Rating Inventory of Executive Function-Adult Self Report Version (BRIEF-A) Total T-score
Time frame: Baseline to week 8
Improvement in ADHD Symptoms as Assessed by the Clinical Global Impression of Improvement for ADHD (CGI-ADHD-I)
Time frame: Week 8
Improvement in Anxiety Symptoms as Assessed by the Clinical Global Impression of Improvement for Anxiety (CGI-Anxiety-I)
Time frame: Week 8
Improvement in Depression Symptoms as Assessed by the Clinical Global Impression of Improvement for Depression (CGI-Depression-I)
Time frame: Week 8
Change From Baseline in Hamilton Anxiety Scale (HAM-A)
Time frame: Baseline to week 8
Change From Baseline in Hamilton Depression Scale (HAM-D)
Time frame: Baseline to week 8
Change From Baseline in Massachusetts General Hospital Social Emotional Competence Scale (MGH-SEC)
Time frame: Baseline to week 8
Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)
Time frame: Baseline to week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundAchenbach, T. M. and L. A. Rescorla (2003). Manual for ASEBA Adult Forms & Profiles. Burlington, VT, University of Vermont, Research Center for Children, Youth, & Families.
- Background: PubMed 16923651Adler LA, Spencer T, Faraone SV, Kessler RC, Howes MJ, Biederman J, Secnik K. Validity of pilot Adult ADHD Self- Report Scale (ASRS) to Rate Adult ADHD symptoms. Ann Clin Psychiatry. 2006 Jul-Sep;18(3):145-8. doi: 10.1080/10401230600801077.
- BackgroundAmerican Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA, American Psychiatric Publishing.
- Background: PubMed 20705131Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun. 2011 Jan;25(1):40-5. doi: 10.1016/j.bbi.2010.08.003. Epub 2010 Aug 10.
- BackgroundAutism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators and Centers for Disease Control and Prevention (2012).
- Background: PubMed 24988818Blumberg SJ, Bramlett MD, Kogan MD, Schieve LA, Jones JR, Lu MC. Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011-2012. Natl Health Stat Report. 2013 Mar 20;(65):1-11, 1 p following 11.
- Background: PubMed 26356811Cassano P, Cusin C, Mischoulon D, Hamblin MR, De Taboada L, Pisoni A, Chang T, Yeung A, Ionescu DF, Petrie SR, Nierenberg AA, Fava M, Iosifescu DV. Near-Infrared Transcranial Radiation for Major Depressive Disorder: Proof of Concept Study. Psychiatry J. 2015;2015:352979. doi: 10.1155/2015/352979. Epub 2015 Aug 19.
- Background: PubMed 26989758Cassano P, Petrie SR, Hamblin MR, Henderson TA, Iosifescu DV. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis. Neurophotonics. 2016 Jul;3(3):031404. doi: 10.1117/1.NPh.3.3.031404. Epub 2016 Mar 4.
- BackgroundConstantino, J. N. and C. P. Gruber (2012). The Social Responsiveness Scale Manual, Second Edition (SRS-2). Los Angeles, CA, Western Psychological Services.
- Background: PubMed 12626762Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buchmann EV, Kane M, Whelan NT, Whelan HT. Therapeutic photobiomodulation for methanol-induced retinal toxicity. Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3439-44. doi: 10.1073/pnas.0534746100. Epub 2003 Mar 7.
- Background: PubMed 8290681Endicott J, Nee J, Harrison W, Blumenthal R. Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol Bull. 1993;29(2):321-6.
- BackgroundEndicott, J., R. L. Spitzer, J. L. Fleiss and J. Cohen (1976).
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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.
T. Atilla Ceranoglu, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Photobiomodulation (tPBM) in people with Autism Spectrum Disorder, run by Massachusetts General Hospital at 1 site in United States.
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 8 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 27 Jan 2026. 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 United States. 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?
Yes. Results are posted in the registry (first posted 27 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Participant Improvement in ASD Symptoms as Assessed by the Clinical Global Impression of Improvement for Autism Spectrum Disorder (CGI-ASD-I) (time frame: Week 8). The study lists 3 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 NCT05363982, which also lists 33 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 27 Jan 2026.