Clinical trial NCT04895605: An Evaluation of Low Level Laser Light Therapy for Autistic Disorder 2
Official title: A Double-blind, Placebo-controlled Randomized Evaluation of the Effect of the Erchonia® HLS Laser Device on Children With Autistic Disorder Clinical Study Protocol 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Conditions: Autistic Disorder
Keywords: Autism
Autistic Disorder
Irritability
laser
light therapy
Lead sponsor: Erchonia Corporation
Sponsor class: INDUSTRY
First posted: 2021-05-20
Enrollment: 40
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the Erchonia HLS Laser is effective in the treatment of irritability associated with autistic disorder in children and adolescents aged five (5) to twelve (12) years.

Detailed description: Autism spectrum disorder (ASD) is a range of complex neurodevelopment disorders characterized by behavioral, developmental, cognitive and psychological deficits that include social impairment, communication and language difficulties, hyperactivity, irritability, obsessive interests and restricted, and repetitive behaviors. Autistic disorder, sometimes called autism or classical ASD, is the most severe form of ASD. ASD occurs in all ethnic and socioeconomic groups and affects every age group, with symptoms appearing before age 3. The Centers for Disease Control (CDC) estimates that 1 out of 88 children age 8 will have an ASD, with males four times more likely to have an ASD than females.

There is no cure for ASD and no single best treatment for all individuals with autistic disorder. The majority of diagnosed cases of autism are idiopathic with an enigmatic pathogenesis, and as a result, therapeutic approaches have focused on mitigating specific symptoms rather than treating disease etiologies. The current standard treatment approach is a team approach to customize an individual highly structured, specialized program or treatment plan including medications, therapies and behavioral interventions targeted toward improving the individual's specific symptoms.

The cause of ASD is not clearly understood, but it is believed that both genetics and environment likely play a role. Magnetic resonance imaging (MRI) studies have demonstrated increased brain volume and head circumference during early developmental childhood, suggesting that autistic brains experience a period a rapid overgrowth which hampers further development during later developmental stages. Morphological aberrations have been observed in the hippocampus, anterior cingulate cortex, prefrontal cortex, amygdala, and cerebellum. Another consistent observation has also been the reduction in cerebellar vermis volume, which helps to explain specific behavioral patterns in children.

Molecular analysis of postmortem brain tissue has revealed reduced Purkinje cell numbers, which helps to explain aberrant locomotive activity and level presser function. Another finding has been impaired neuronal connectivity within the cerebellum, amygdala, anterior cingulate cortex, and dorsolateral prefrontal cortex. As a consequence, synapse structure and function has demonstrated impairment in postmortem evaluations. Dendritic spines of glutamatergic neurons in autistic patients have shown morphological alterations and suppressed density, which, in turn, results in diminished synaptic transmissions. Nascent spines have been reported in frontal, temporal, and parietal cortices of autistic patients, and have a negative correlation with cognitive abilities in autism. Other neurological aberrations include signaling through metabotropic glutamate receptor (mGluR) and ƴ-aminobutyric acid (GABA)ergic system.

The elusive pathophysiology of autism provides a marked challenge for health care providers. One promising technology is low-level laser therapy (LLLT). LLLT uses photonic energy to modulate the behavior and function of cells by stimulating molecular entities capable of absorbing discrete wavelengths. or instance, cytochrome c oxidase (CCO), a terminal enzyme of the respiratory change, contains a tetrapyrrole prosthetic group that has been shown to absorb 635nm. Photon-induced activation of CCO increases cell bioenergetics, which, in turn, activates intra-cellular secondary signaling cascades that in turn affect growth factor synthesis, cell proliferation, cytokine production, and expression of specific transcription factors. Studies have reported increased adenosine triphosphate (ATP) synthesis along with activation of the intracellular redox state following the production of reactive oxygen species (ROS). As an essential bio-catalyst, ATP lowers the activation for pivotal biochemical reactions within cells. Concerning neurons, laser irradiation has been shown to promote the recovery of injured peripheral nerves and the spinal cord. Moreover, studies have revealed that excitable cells like neurons can be directly stimulated by light, enhancing the action potential of the cell increasing the release of neurotransmitters such as glutamate and acetylcholine.

Clinical outcomes with LLLT trials include nerve regeneration, increased neurotransmitter release, growth factor synthesis, and neovascularization to name a few. It follows that positioning of the laser along impaired regions of an autistic brain could elicit a positive therapeutic outcome in a safe and non-invasive manner.

Eligibility criteria: Inclusion Criteria:

* Male or female child or adolescent aged 5 to 12 years
* Subject has met Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) for autistic disorder within the past 2 years, as diagnosed by a trained, qualified medical professional such as a pediatric neurologist, child psychiatrist or developmental pediatrician Diagnosis is confirmed by Autism Diagnostic Interview (ADI-R)
* Subject demonstrates 'irritable' behaviors such as tantrums, aggression, self-injurious behavior, or a combination of such behaviors
* Subject's Aberrant Behavior Checklist (ABC) Irritability Subscale score is \>=18
* Subject's Clinical Global Impressions - Severity (CGI-S) scale score is \>=4 (4=moderately ill)
* Subject's current therapeutic/intervention plan for treating his or her autistic disorder (educational/behavioral or other therapy; medication use; dietary interventions) has been consistent/stable over at least the past 3 months and the subject's caregiver agrees, and it is possible for, the subject to maintain his or her current therapeutic/intervention plan throughout participation in the clinical study.
* Subject's caregiver agrees, and it is possible for, the subject to abstain from partaking in new treatments to treat the subject's autistic disorder symptoms during participation in the study. This includes educational/behavioral therapy, dietary interventions, medications such as FDA-approved Risperdal® and Abilify® and other medications often prescribed for the treatment of other autism-related symptoms, such as anxiety, depression, or obsessive-compulsive disorder, including antipsychotic medications used to treat severe behavioral problem, and medications used to treat people with attention deficit disorder

Exclusion Criteria:

* Subject has a primary or concurrent diagnosis of another disorder or other identifiable genetic condition associated with the autism spectrum scale or with mental retardation, including:

PDD-NOS Asperger's Disorder Rett's Disorder Fragile-X Syndrome Childhood Disintegrative Disorder Down Syndrome

* Seizure disorders (active), cerebrovascular disease or brain trauma as etiology of autistic behavior
* Current diagnosis of, and treatment for, bipolar disorder, psychosis, schizophrenia, or major depression
* Known neurological disease, such as encephalitis
* Significant sensory or motor impairment such as cerebral palsy
* Diagnosis of epilepsy that is currently treated with anti-convulsant medication
* Previous significant head trauma
* Hearing loss requiring use of assistive devices such as hearing aids or cochlear implant
* Significant visual impairment that cannot be adequately corrected with lenses
* Documented mental age younger than 18 months
* HIV and other autoimmune disorders
* Active cancer or treatment for cancer within last 6 months
* Unstable cardiac disease, such as a recent cardiac arrhythmia (including atrial fibrillation, ventricular fibrillation and irregular atrial-ventricular conduction time), or recent congestive heart failure, or recent myocardial infarction
* Previous surgical interventions to the head/neck area
* Sensitivity to, or contraindication for, light therapy
* Participation in a research study within the past 30 days

Primary outcomes:
measure: Mean Change From Baseline to Study Endpoint in the Aberrant Behavior Checklist (ABC) Irritability & Agitation Subscale Score.
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
Study officials:
References: