Evaluation of Transcranial Photobiomodulation in Autism Spectrum Disorder: Double-Blind, Placebo-Controlled, Randomized Clinical Study of a Novel Approach
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Participant Improvement in ASD Symptoms as Assessed by the Clinical Global Impression of Improvement for Autism Spectrum Disorder (CGI-ASD-I)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Transcranial Photobiomodulation (tPBM) Treatment
Transcranial Photobiomodulation--a noninvasive intervention in which near-infrared light is applied to forebrain.
干预措施: Transcranial Photobiomodulation (tPBM) (Device)
Placebo/ Sham Treatment
The sham treatment will mimic the tPBM procedure, while delivering no light.
干预措施: Placebo/ Sham (Device)
结局指标
主要结局
Participant Improvement in ASD Symptoms as Assessed by the Clinical Global Impression of Improvement for Autism Spectrum Disorder (CGI-ASD-I)
时间窗: 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
时间窗: 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)
时间窗: 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).
次要结局
- Change From Baseline in Adult Behavior Checklist (ABCL) Total T-score(Baseline to week 8)
- Change From Baseline in Adult ADHD Investigator Symptom Report Scale (AISRS)(Baseline to week 8)
- Change From Baseline in Adult ADHD Self-Report Scale (ASRS)(Baseline to week 8)
- Change From Baseline in Behavior Rating Inventory of Executive Function-Adult Self Report Version (BRIEF-A) Total T-score(Baseline to week 8)
- Improvement in ADHD Symptoms as Assessed by the Clinical Global Impression of Improvement for ADHD (CGI-ADHD-I)(Week 8)
- Improvement in Anxiety Symptoms as Assessed by the Clinical Global Impression of Improvement for Anxiety (CGI-Anxiety-I)(Week 8)
- Improvement in Depression Symptoms as Assessed by the Clinical Global Impression of Improvement for Depression (CGI-Depression-I)(Week 8)
- Change From Baseline in Hamilton Anxiety Scale (HAM-A)(Baseline to week 8)
- Change From Baseline in Hamilton Depression Scale (HAM-D)(Baseline to week 8)
- Change From Baseline in Massachusetts General Hospital Social Emotional Competence Scale (MGH-SEC)(Baseline to week 8)
- Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)(Baseline to week 8)
研究者
Tolga A Ceranoglu
Associate Psychiatrist
Massachusetts General Hospital