Clinical trial NCT03859336: High-Frequency Transdermal Neuromodulation to Decrease Anxiety and Improve Sleep in ASD
Official title: High-Frequency Transdermal Neuromodulation to Decrease Anxiety and Improve Sleep in Autism Spectrum Disorder (ASD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: Anxiety
Sleep Issues
Lead sponsor: Phoenix Children's Hospital
Sponsor class: OTHER
First posted: 2019-03-01
Enrollment: 10
Sex: ALL
Minimum age (years): 10
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective 3 day open-label device trial across all subjects, with 1 day single-blinded sham pre- and post-treatment
Primary purpose: TREATMENT

Brief summary: The objective of this study is to investigate the feasibility of cervical TEN stimulation (TENS) delivered to the back of the neck to decrease anxiety and sleep issues in young adults with Autism Spectrum Disorder (ASD). The specific aim is to determine the effect of TENS, delivered over 3 daily sessions, on anxiety and sleep quality in young adults with ASD, as compared to sham and baseline. The investigator will enroll up to 10 young adults, aged 10 to 25 years of age with confirmed ASD and measureable anxiety and sleep disturbance symptoms, and participation will last 3 weeks.

Detailed description: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with life-long consequences that affects children during critical times in their development. ASD is associated with co-occurring problems such as anxiety and sleep disturbances. New approaches to managing stress, anxiety, and sleep quality would greatly enhance the quality of life and activities of daily living for children with ASD as they transition to adulthood and age out of services. Based on strong evidence from typically developing individuals, the technology for transdermal electrical neuromodulation (TEN) of the cranial nerves has shown to be a safe, effective, comfortable, and non-pharmacological therapy to modulate the central nervous system decreasing anxiety and enhancing sleep quality to improve the quality of life for people with ASD.

The therapy applies tuned, high-frequency TEN to the back of the neck which activates the brainstem modulating noradrenergic signaling shown to decrease anxiety in healthy adults. The low-amplitude of the stimulation means that it is painless and comfortable. Furthermore, the technology is being evaluated for improving sleep quality. The mechanism of these effects are well established in the neurophysiology literature, but modulating these brainstem areas is only now possible non-invasively with the technology. Participants entered into the trial wil have anxiety and sleep issues that are known to be associated with ASD. The investigators hypothesize that cervical TEN will decrease anxiety and improve sleep quality in a population with high-functioning ASD who are transitioning into adulthood.

The investigators will study 10 young adults, between the ages of 10 years to 25 years, with confirmed ASD and anxiety and sleep quality issues. All participants will be enrolled in the study for approximately 2 weeks. During the first week, participants will undergo 5 consecutive days of stimulation. On Visit 1, all participants will receive sham stimulation, which will be used to exclude placebo responders and those who cannot tolerate study procedures, and determine the maximum stimulation threshold for eligible participants. Additionally, the visit will serve as the baseline day to collect measures of anxiety. The primary physiological anxiety measures include galvanic skin response (GSR) and heart rate variability (HRV). Secondary measures will include data from behavioral surveys, and cortisol and amylase analyses from passive drool samples. Participants will report baseline sleep habits in the form of a questionnaire.

If all eligibility criteria are met, participants will return for 3 consecutive days of open label TEN stimulation treatment. Anxiety measures will be collected at each visit. On the fifth consecutive day, participants will once again receive sham stimulation in order to determine the impact of the open label treatment. Participation will conclude with a one day phone follow-up visit one week from the last treatment day. Caregivers will report participant sleep quality and any adverse effects or changes.

Eligibility criteria: Inclusion Criteria:

* Between the age of 10 - 25 years old
* IQ \> 80, to be evaluated during the screening visit using the Kaufman Brief Intelligence Test (KBIT)
* Self-reported complaints about anxiety and/or sleep issues
* Screen for Child Anxiety Related Disorders (SCARED) - Parent Form, score \>= 25
* Able to follow directions in English

Exclusion Criteria:

* • IQ ≤ 80, to be evaluated during the screening visit using the KBIT
* SCARED - Parent Form, Score \< 25
* Has a medical implant (such as a pacemaker, cochlear implant, brain stimulation device, spinal stimulator)
* History of significant face/head injury including cranial or facial metal plate or screw implants
* Pregnant
* History of migraines or frequent headaches (more than once a week)
* Started taking anti-anxiety medications less than 3 months prior to study participation or has not been taking anti-anxiety medications consistently for at least 3 months prior to study participation
* Fainting (vaso-vagal syncope or neurocardiogenic syncope)
* Diagnosis of Raynaud's disease
* Tempromandibular joint (TMJ) disorder or other facial neuropathy
* Poor vision or hearing that is uncorrectable
* Seizures in the last 2 years
* Evidence of skin disease or skin abnormalities affecting the neck or upper back
* Upper extremity contractures

Primary outcomes:
measure: Change in physiological response measure of heart rate variability in the time-domain as measured by the standard deviation of the normal-to-normal heart beat (SDNN)
timeFrame: Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)
measure: Change in physiological response measure of heart rate variability in the frequency-domain as measured by the power of the low frequency (LF) band
timeFrame: Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)
measure: Change in physiological response measure of heart rate variability in the frequency-domain as measured by the power of the high frequency (HF) band
timeFrame: Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)
measure: Change in physiological response measure of galvanic skin response (GSR)
timeFrame: Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)
Secondary outcomes:
measure: Change in the Screen for Child Anxiety Related Disorders (SCARED) score
timeFrame: Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)
measure: Change in the Parent Reported Anxiety Scale (PRAS) score
timeFrame: Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)
measure: Change in amylase and cortisol levels
timeFrame: Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)
measure: Change in the Children's Sleep Habits Questionnaire (CSHQ) score
timeFrame: Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5), Follow-Up (1 week following sham visit)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
Study officials:
affiliation: Phoenix Children's Hospital
name: Richard E Frye, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tyler WJ, Boasso AM, Mortimore HM, Silva RS, Charlesworth JD, Marlin MA, Aebersold K, Aven L, Wetmore DZ, Pal SK. Transdermal neuromodulation of noradrenergic activity suppresses psychophysiological and biochemical stress responses in humans. Sci Rep. 2015 Sep 10;5:13865. doi: 10.1038/srep13865.
citation: Boasso AM, Mortimore H, Silva R, Aven L, Tyler, WJ. Transdermal electrical neuromodulation of the trigeminal sensory nuclear complex improves sleep quality and mood. BioRxiv. 2016 Jan 1. doi: 10.1101/043901
citation: Carter ME, Yizhar O, Chikahisa S, Nguyen H, Adamantidis A, Nishino S, Deisseroth K, de Lecea L. Tuning arousal with optogenetic modulation of locus coeruleus neurons. Nat Neurosci. 2010 Dec;13(12):1526-33. doi: 10.1038/nn.2682. Epub 2010 Oct 31.
citation: van Steensel FJA, Heeman EJ. Anxiety Levels in Children with Autism Spectrum Disorder: A Meta-Analysis. J Child Fam Stud. 2017;26(7):1753-1767. doi: 10.1007/s10826-017-0687-7. Epub 2017 Mar 20.
citation: White SW, Oswald D, Ollendick T, Scahill L. Anxiety in children and adolescents with autism spectrum disorders. Clin Psychol Rev. 2009 Apr;29(3):216-29. doi: 10.1016/j.cpr.2009.01.003. Epub 2009 Jan 25.