An Evaluation of Low Level Laser Light Therapy for Autistic Disorder

• Sponsor: Erchonia Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03379662
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Actual Duration (Months): 4.9
• Patients Per Site Per Month: 8.2

Study Details

Study Description

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 seventeen (17) years.

Condition or Disease	Intervention/Treatment	Phase
Autistic Disorder	Device: Erchonia HLS Laser; Device: Placebo Laser	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo-controlled Randomized Evaluation of the Effect of the Erchonia® HLS Laser Device on Children and Adolescents With Autistic Disorder
• Actual Study Start Date: Jul 2, 2017
• Actual Primary Completion Date: Oct 28, 2017
• Actual Study Completion Date: Nov 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erchonia HLS Laser The Erchonia HLS Laser is administered 8 times across 4 weeks for 5 minutes each time to the skull at the base of the brain and temporal areas.	Device: Erchonia HLS Laser; The Erchonia HLS Laser emits a 640 nm (nanometer) wavelength with a tolerance of ±10 nm from each of two 7.5 mw (milliwatt) laser diodes.
Placebo Comparator: Placebo Laser The Placebo Laser is administered 8 times across 4 weeks for 5 minutes each time to the skull at the base of the brain and temporal areas.	Device: Placebo Laser; The Placebo Laser emit the same visible light output as the active HLS Laser but without therapeutic effect.

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline to Study Endpoint in the Aberrant Behavior Checklist (ABC) Irritability & Agitation Subscale Score. [Baseline and 4 weeks (Study Endpoint)]

   Primary outcome measure in this study is defined as the mean change from baseline to 4 weeks of intervention (study endpoint), in the Aberrant Behavior Checklist (ABC) Irritability Subscale score. The ABC Irritability Subscale contains 15 items relating to aggression, self-injury, tantrums, agitation and unstable mood in individuals with developmental disorders. Each item is rated from 0 (not at all a problem) to 3 (the problem is severe in degree). The individual scores are summed for a total score from 0 to 45, with higher scores indicating greater severity. A negative (-) change indicates a decrease in symptom severity and is positive for improvement. A positive (+) change indicates an increase in symptom severity and is negative for improvement. Study success is established as the detection of a minimum mean difference of -8.5 points between test and placebo groups in the change in ABC Irritability Subscale score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female child or adolescent aged 5 to 17 years

• Meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria (DSM-IV-TR) 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)

• Demonstrates 'irritable' behaviors such as tantrums, aggression, self-injurious behavior, or a combination of such behaviors

• Aberrant Behavior Checklist (ABC) Irritability Subscale score is >=18

• Clinical Global Impressions - Severity (CGI-S) scale score is >=4 (moderately ill)

• Current therapeutic/intervention plan for treating autistic disorder has been consistent/ stable over at least the past 3 months

• Caregiver agrees, and it is possible for, the subject to abstain from partaking in new treatments to treat autistic disorder symptoms during the course of study participation

• Female subjects of child-bearing age are willing and able to use acceptable means of contraception throughout study participation.

Exclusion Criteria:

• Primary or concurrent diagnosis of another disorder or other identifiable genetic condition associated with the autism spectrum scale or with mental retardation, including:

Pervasive Developmental Disorder-Not Otherwise Specified (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

• Current use of a psychotropic drug deemed effective for the treatment of aggression, tantrums or self-injurious behavior

• 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 arrhythmias (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

• Subject is presently pregnant or breast feeding

• Participation in a research study within the past 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute for Brain and Rehabilitation Sciences	Nazareth		Israel	16470

Sponsors and Collaborators

• Erchonia Corporation

Investigators

• Principal Investigator: Calixto Machado, MD,

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jan 31, 2013

More Information

Publications

None provided.

• Responsible Party: Erchonia Corporation
• ClinicalTrials.gov Identifier: NCT03379662
• Other Study ID Numbers: EC_AUT_001
• First Posted: Dec 20, 2017
• Last Update Posted: May 27, 2021
• Last Verified: May 1, 2021

• 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.: Yes
• Keywords provided by Erchonia Corporation: Autism; Autistic Disorder; Autistic Spectrum Disorder; Irritability; laser; light therapy
• Additional relevant MeSH terms: Disease; Autistic Disorder

Study Results

Participant Flow

Arm/Group Title	Erchonia HLS Laser	Placebo Laser
Arm/Group Description	The Erchonia HLS Laser is administered 8 times across 4 weeks for 5 minutes each time to the skull at the base of the brain and temporal areas. Erchonia HLS Laser: The Erchonia HLS Laser emits a 640 nm (nanometer) wavelength with a tolerance of ±10 nm from each of two 7.5 mw (milliwatt) laser diodes.	The Placebo Laser is administered 8 times across 4 weeks for 5 minutes each time to the skull at the base of the brain and temporal areas. Placebo Laser: The Placebo Laser emit the same visible light output as the active HLS Laser but without therapeutic effect.
Period Title: Overall Study
STARTED	21	19
COMPLETED	21	19
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Erchonia HLS Laser	Placebo Laser	Total
Arm/Group Description	The Erchonia HLS Laser is administered 8 times across 4 weeks for 5 minutes each time to the skull at the base of the brain and temporal areas. Erchonia HLS Laser: The Erchonia HLS Laser emits a 640 nm (nanometer) wavelength with a tolerance of ±10 nm from each of two 7.5 mw (milliwatt) laser diodes.	The Placebo Laser is administered 8 times across 4 weeks for 5 minutes each time to the skull at the base of the brain and temporal areas. Placebo Laser: The Placebo Laser emit the same visible light output as the active HLS Laser but without therapeutic effect.	Total of all reporting groups
Overall Participants	21	19	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.24 (3.02)	8.37 (3.15)	8.29 (3.07)
Sex: Female, Male (Count of Participants)
Female	5 23.8%	5 26.3%	10 25%
Male	16 76.2%	14 73.7%	30 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 5.3%	1 2.5%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	8 38.1%	12 63.2%	20 50%
White	12 57.1%	4 21.1%	16 40%
More than one race	1 4.8%	2 10.5%	3 7.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Cuba	21 100%	19 100%	40 100%
Baseline Aberrant Behavior Checklist (ABC) Irritability Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	30.52 (15.71)	29.58 (28.89)	30.04 (22.65)

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline to Study Endpoint in the Aberrant Behavior Checklist (ABC) Irritability & Agitation Subscale Score.
Description	Primary outcome measure in this study is defined as the mean change from baseline to 4 weeks of intervention (study endpoint), in the Aberrant Behavior Checklist (ABC) Irritability Subscale score. The ABC Irritability Subscale contains 15 items relating to aggression, self-injury, tantrums, agitation and unstable mood in individuals with developmental disorders. Each item is rated from 0 (not at all a problem) to 3 (the problem is severe in degree). The individual scores are summed for a total score from 0 to 45, with higher scores indicating greater severity. A negative (-) change indicates a decrease in symptom severity and is positive for improvement. A positive (+) change indicates an increase in symptom severity and is negative for improvement. Study success is established as the detection of a minimum mean difference of -8.5 points between test and placebo groups in the change in ABC Irritability Subscale score.
Time Frame	Baseline and 4 weeks (Study Endpoint)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erchonia HLS Laser	Placebo Laser
Arm/Group Description	The Erchonia HLS Laser is administered 8 times across 4 weeks for 5 minutes each time to the skull at the base of the brain and temporal areas. Erchonia HLS Laser: The Erchonia HLS Laser emits a 640 nm (nanometer) wavelength with a tolerance of ±10 nm from each of two 7.5 mw (milliwatt) laser diodes.	The Placebo Laser is administered 8 times across 4 weeks for 5 minutes each time to the skull at the base of the brain and temporal areas. Placebo Laser: The Placebo Laser emit the same visible light output as the active HLS Laser but without therapeutic effect.
Measure Participants	21	19
Mean (Standard Deviation) [score on a scale]	-14.81 (6.40)	0.37 (1.38)

Adverse Events

Time Frame	4 weeks
Arm/Group Title	Erchonia HLS Laser		Placebo Laser
Arm/Group Description	The Erchonia HLS Laser is administered 8 times across 4 weeks for 5 minutes each time to the skull at the base of the brain and temporal areas. Erchonia HLS Laser: The Erchonia HLS Laser emits a 640 nm (nanometer) wavelength with a tolerance of ±10 nm from each of two 7.5 mw (milliwatt) laser diodes.		The Placebo Laser is administered 8 times across 4 weeks for 5 minutes each time to the skull at the base of the brain and temporal areas. Placebo Laser: The Placebo Laser emit the same visible light output as the active HLS Laser but without therapeutic effect.
All Cause Mortality
	Erchonia HLS Laser		Placebo Laser
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/19 (0%)
Serious Adverse Events
	Erchonia HLS Laser		Placebo Laser
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Erchonia HLS Laser		Placebo Laser
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.