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

NCT ID: NCT03859336

Last Updated: 2021-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-21

Study Completion Date

2021-10-06

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Autism Spectrum Disorder

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Anxiety Sleep Issues

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Prospective 3 day open-label device trial across all subjects, with 1 day single-blinded sham pre- and post-treatment
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Transdermal Neuromodulation Stimulation

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.

Group Type EXPERIMENTAL

Transdermal Neuromodulation Stimulation

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Transdermal Neuromodulation Stimulation

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.

Intervention Type DEVICE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

10 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Phoenix Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Richard Frye, MD, PhD

Chief of Neurodevelopmental Disorders at Barrow Neurological Institute

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Richard E Frye, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Phoenix Children's Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 26353920 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 21037585 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28680259 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19223098 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

TENS_ASD

Identifier Type: -

Identifier Source: org_study_id