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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
41
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
The sham treatment will consist of applying all the procedures for the delivery of tPBM, but will not deliver light.
Massachusetts General Hospital
Boston, Massachusetts, United States
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.
Time frame: 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.
Time frame: 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).
Time frame: Baseline to week 8
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).
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Time frame: 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).
Time frame: 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).
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
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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: Baseline to week 8