Evaluation of Transcranial Photobiomodulation in Autism Spectrum Disorder

January 23, 2026 updated by: Tolga A Ceranoglu, Massachusetts General Hospital

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

41

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 59 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Transcranial Photobiomodulation (tPBM) Treatment
Transcranial Photobiomodulation--a noninvasive intervention in which near-infrared light is applied to forebrain.
Device: 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
Sham Comparator: Placebo/ Sham Treatment
The sham treatment will mimic the tPBM procedure, while delivering no light.
Device: Placebo/ Sham
The sham treatment will consist of applying all the procedures for the delivery of tPBM, but will not deliver light.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 8
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.
Week 8
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).
Baseline to week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Adult Behavior Checklist (ABCL) Total T-score
Time Frame: Baseline to week 8
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).
Baseline to week 8
Change From Baseline in Adult ADHD Investigator Symptom Report Scale (AISRS)
Time Frame: Baseline to week 8
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).
Baseline to week 8
Change From Baseline in Adult ADHD Self-Report Scale (ASRS)
Time Frame: Baseline to week 8
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).
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
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).
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
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.
Week 8
Improvement in Anxiety Symptoms as Assessed by the Clinical Global Impression of Improvement for Anxiety (CGI-Anxiety-I)
Time Frame: Week 8
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.
Week 8
Improvement in Depression Symptoms as Assessed by the Clinical Global Impression of Improvement for Depression (CGI-Depression-I)
Time Frame: Week 8
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.
Week 8
Change From Baseline in Hamilton Anxiety Scale (HAM-A)
Time Frame: Baseline to week 8
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).
Baseline to week 8
Change From Baseline in Hamilton Depression Scale (HAM-D)
Time Frame: Baseline to week 8
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).
Baseline to week 8
Change From Baseline in Massachusetts General Hospital Social Emotional Competence Scale (MGH-SEC)
Time Frame: Baseline to week 8
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).
Baseline to week 8
Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)
Time Frame: Baseline to week 8
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).
Baseline to week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: T. Atilla Ceranoglu, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2022

Primary Completion (Actual)

October 31, 2024

Study Completion (Actual)

October 31, 2024

Study Registration Dates

First Submitted

April 27, 2022

First Submitted That Met QC Criteria

May 2, 2022

First Posted (Actual)

May 6, 2022

Study Record Updates

Last Update Posted (Actual)

January 27, 2026

Last Update Submitted That Met QC Criteria

January 23, 2026

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021- P- 002646

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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