Evaluation of Transcranial Photobiomodulation in Autism Spectrum Disorder

Autism Spectrum Disorder Clinical Trial

Official title: Evaluation of Transcranial Photobiomodulation in Autism Spectrum Disorder: Double-Blind, Placebo-Controlled, Randomized Clinical Study of a Novel Approach

Status Recruiting

Clinical 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive

• NCT number: NCT05363982
• Study type: Interventional
• Source: Massachusetts General Hospital
• Contact: Chloe Hutt Vater, BA
• Phone: 617-724-7301
• Email: chuttvater@mgh.harvard.edu
• Status: Recruiting
• Phase: N/A
• Start date: February 11, 2022
• Completion date: February 11, 2025