High-Frequency Transdermal Neuromodulation to Decrease Anxiety and Improve Sleep in ASD

NCT03859336 | Completed FDA Device

• 1 other identifier: TENS_ASD
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism Spectrum Disorder

Keywords

Anxiety; Sleep Issues

Outcome Measures

Primary Outcomes (4)

• 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)

  The standard deviation of the normal-to-normal heart beat (SDNN) is the time-domain based measured of heart rate variability. It is measured by calculating the standard deviation of the heart beat-to-beat time interval, which is measured in milliseconds. Anxiety reduction will be demonstrated by a reduction in the SDNN value during a stressor in response to TEN treatment, as compared to baseline.

  Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)

• Change in physiological response measure of heart rate variability in the frequency-domain as measured by the power of the low frequency (LF) band

  The low frequency (LF) component of heart rate variability (HRV) is the frequency band ranging from 0.04-0.15Hz of the waveform created by heart rate oscillations. Spectral power is calculated for this band in milliseconds squared. Anxiety reduction will be demonstrated by a reduction in the power value of the LF HRV component during a stressor in response to TEN treatment, as compared to baseline.

  Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)

• Change in physiological response measure of heart rate variability in the frequency-domain as measured by the power of the high frequency (HF) band

  The high frequency (HF) component of heart rate variability (HRV) is the frequency band ranging from 0.15-0.4Hz of the waveform created by heart rate oscillations. Spectral power is calculated for this band in milliseconds squared. Anxiety reduction will be demonstrated by a reduction in the power value of the HF HRV component during a stressor in response to TEN treatment, as compared to baseline.

  Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)

• Change in physiological response measure of galvanic skin response (GSR)

  Galvanic skin response (GSR) is an electrodermal conductance measurement that reflects the changes in sweat gland activity, which is measured in microsiemens (μS). Anxiety reduction will be analyzed through a suppression of GSR activity value during a stressor in response to TEN treatment, as compared to baseline data.

  Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)

Secondary Outcomes (4)

• Change in the Screen for Child Anxiety Related Disorders (SCARED) score

  Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)

• Change in the Parent Reported Anxiety Scale (PRAS) score

  Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)

• Change in amylase and cortisol levels

  Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5)

• Change in the Children's Sleep Habits Questionnaire (CSHQ) score

  Baseline Visit (Day 1), Treatment Visits (Days 2, 3, and 4), Sham Visit (Day 5), Follow-Up (1 week following sham visit)

Study Arms (1)

Transdermal Neuromodulation Stimulation

EXPERIMENTAL

Day 1 of Transdermal Neuromodulation Stimulation (TENS) is a one-day sham stimulation, consisting of: 30 seconds of sensation in which amplitude is increased up to the threshold of salient sensation, followed by 19 minutes of no stimulation (device is turned off), followed by 30 more seconds of salient stimulation. Day 1 is used to exclude those who cannot tolerate study procedures and placebo responders; it will also serve as baseline for anxiety measures. TENS treatment begins one day after sham, and lasts 3 days with 20 minutes of stimulation per day. One day following open label treatment all participants will once again receive sham stimulation following the same procedures utilized at Day 1. Treatment amplitude is adjusted for each participant, in which the stimulation will be administered just below the participant's sensation threshold. Amplitude from the TENS device does not exceed 20mA. Frequency will be at 300hz.

Device: Transdermal Neuromodulation Stimulation

Interventions

Transdermal Neuromodulation Stimulation DEVICE

The TEN device administers a tuned high frequency electrical stimulation delivered to the cervical plexus (C2-C4) on the back of the neck for 20 minutes. This stimulation will activate common trigeminovagal pathways modulating noradrenergic signaling to attenuate sympathetic activity. This stimulation can subsequently regulate the activity of several deep-brain nuclei within the ascending reticular activating system (RAS). Nuclei in the RAS regulate powerful neuromodulators like norepinephrine (NE), acetylcholine (ACh), and serotonin (5-HT). The investigators will examine whether this modulation from TENS will decrease anxiety and improve sleep quality in the study participants.

Transdermal Neuromodulation Stimulation

Eligibility Criteria

• Age: 10 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Phoenix Children's Hospital: lead

Study Sites (1)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Related Publications (5)

• 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.

  PMID: 26353920 BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 21037585 BACKGROUND

• 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.

  PMID: 28680259 BACKGROUND

• 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.

  PMID: 19223098 BACKGROUND

MeSH Terms

Conditions

Autism Spectrum Disorder; Anxiety Disorders

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Richard E Frye, MD, PhD

  Phoenix Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Neurodevelopmental Disorders at Barrow Neurological Institute

Model Details: Prospective 3 day open-label device trial across all subjects, with 1 day single-blinded sham pre- and post-treatment

Study Record Dates

• First Submitted: February 21, 2019
• First Posted: March 1, 2019
• Study Start: May 21, 2019
• Primary Completion: July 19, 2021
• Study Completion: October 6, 2021
• Last Updated: December 20, 2021

Record last verified: 2021-12

Locations

US (1)