eTNS for ADHD

Recruiting at 1 trial location

Overseen By Mark Stein, Ph.D.

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must not be taking: CNS medications

Disqualifiers: Autism, Major depression, Psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

280 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a treatment called TNS, which sends a small electrical signal to the forehead during sleep, in children aged 7-12 with ADHD. The signal helps activate brain areas that improve attention and impulse control.

Will I have to stop taking my current medications?

Yes, participants must stop taking any current medications that affect the central nervous system (CNS). If they were on psychostimulant medication, they need to be off it for one week or 5 half-lives of the medication.

What data supports the effectiveness of the treatment eTNS for ADHD?

Research shows that trigeminal nerve stimulation (TNS) may help with ADHD, as a study found potential benefits in an open trial. Additionally, eTNS has been effective in reducing seizures in epilepsy, suggesting it might have positive effects on brain function. ^{1 2 3 4 5}

Is eTNS safe for humans?

Research shows that eTNS is generally safe and well-tolerated in humans, with studies focusing on epilepsy indicating no significant issues with heart rate or blood pressure. ^{2 4 5 6 7}

How is the eTNS treatment for ADHD different from other treatments?

The eTNS treatment for ADHD is unique because it is a non-invasive therapy that uses adhesive skin electrodes to stimulate the trigeminal nerve, unlike traditional medications that are taken orally. This method is similar to its use in epilepsy, where it has shown potential benefits without the need for drugs. ^{1 2 4 5 6}

Research Team

Sandra K. Loo, Ph.D.

Principal Investigator

University of California, Los Angeles

James J. McGough, M.D.

Principal Investigator

University of California, Los Angeles

Mark A. Stein, Ph.D.

Principal Investigator

Seattle Children's Hospital

Eligibility Criteria

This trial is for children aged 7-12 with ADHD, as confirmed by specific diagnostic interviews. They must have a certain level of ADHD symptoms and be able to complete English language assessments and EEG tests. Kids should have an IQ of 80 or above and not be on CNS-affecting meds (though stable supplements are okay). Children with a history of psychosis, mania, seizures, severe head injury, autism spectrum disorder or major depression cannot participate.

Inclusion Criteria

Estimated Full Scale IQ >= 80 based on WASI subtests

CGI-S score at baseline >= 4

I can stay still and cooperate during an EEG test.

Exclusion Criteria

I have been diagnosed with autism or major depression.

Baseline suicidality

History of lifetime psychosis, mania, or seizure disorder

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

4-week double-blind, controlled trial of active vs. sham TNS. Participants use TNS nightly during sleep.

4 weeks

Weekly behavioral ratings and EEG assessments

Treatment Phase 2

Participants initially randomized to sham receive active TNS for an additional 4 weeks, with continued weekly assessments.

4 weeks

Weekly assessments

Follow-up

Brief naturalistic follow-ups via phone or Zoom at months 3 and 6 post-treatment.

6 months

2 visits (virtual)

Open-label extension (optional)

Positive responders to active eTNS are invited to participate in a 12-month open-label continuation phase.

12 months

Treatment Details

Interventions

• eTNS

Trial Overview The study is testing external trigeminal nerve stimulation (eTNS) against a sham (fake) treatment to see if it helps reduce ADHD symptoms in kids over four weeks. It also looks at how brain connectivity and activation might influence the effectiveness of eTNS therapy.

Participant Groups

Group I: Active eTNS Experimental Treatment 1 Intervention

Following screening and determination of eligibility , participants at baseline are randomized to receive 4 weeks nightly treatment with active eTNS. Positive responders will be invited to participate in a 12-month open-label continuation phase.

Group II: Sham eTNS Placebo Group 2 Interventions

Following screening and determination of eligibility, participants at baseline are randomize to receive 4 weeks nightly treatment with sham eTNS. At conclusion of the double-blind phase, participants randomized to sham will be provided an opportunity to receive an additional 4 weeks nightly treatment with active eTNS. Positive responders to active eTNS will be invited to participate in a 12-month open-label continuation phase.

eTNS is already approved in United States for the following indications:

Approved in United States as Monarch eTNS System for:

• Attention-Deficit/Hyperactivity Disorder (ADHD) in children ages 7-12

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

Trigeminal nerve stimulation (TNS) was found to be effective in reducing ADHD symptoms in a blinded sham-controlled trial involving 62 children, showing a significant improvement in ADHD Rating Scales and Clinical Global Impression scores after 4 weeks of treatment.

TNS was well tolerated with no clinically meaningful adverse events reported, indicating it is a safe, minimal-risk option for managing ADHD, with effects comparable to non-stimulant medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-Blind, Sham-Controlled, Pilot Study of Trigeminal Nerve Stimulation for Attention-Deficit/Hyperactivity Disorder. McGough, JJ., Sturm, A., Cowen, J., et al.[2023]

External trigeminal nerve stimulation (ETNS) significantly reduced seizure frequency in patients with focal drug-resistant epilepsy (DRE), with a 50% response rate compared to 0% in the control group after 12 months.

ETNS was well-tolerated with no relevant adverse events, and it improved quality of life without affecting mood or cognitive function, indicating its potential as a safe long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External trigeminal nerve stimulation for drug resistant epilepsy: A randomized controlled trial. Gil-López, F., Boget, T., Manzanares, I., et al.[2021]

Trigeminal nerve stimulation (TNS) showed significant improvements in ADHD symptoms and executive functioning in a study of 24 youth participants aged 7-14 over an 8-week period, indicating its potential as a treatment option.

The therapy was found to be feasible and safe, with no significant risks reported, and it positively affected cognitive tasks related to response inhibition, suggesting further research is warranted to explore its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulation in youth with attention-deficit/hyperactivity disorder. McGough, JJ., Loo, SK., Sturm, A., et al.[2019]

In a study of 42 patients with drug refractory epilepsy, external trigeminal nerve stimulation (eTNS) showed a significant improvement in quality of life and mood for patients without intellectual disabilities, suggesting its potential benefits beyond seizure control.

While there was a decrease in seizure frequency of 11% among participants, this change was not statistically significant, indicating that more controlled studies are needed to fully assess the efficacy of eTNS as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An audit of external trigeminal nerve stimulation (eTNS) in epilepsy. Slaght, SJ., Nashef, L.[2018]

External trigeminal nerve stimulation (eTNS) is a safe and well-tolerated long-term treatment for drug-resistant epilepsy, with no serious device-related adverse events reported over 12 months.

In a follow-up study of 35 participants, eTNS significantly reduced median seizure frequency by 27.4% at 6 months and 34.8% at 12 months, demonstrating its efficacy as a promising therapy for patients with epilepsy who do not respond to medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective long-term study of external trigeminal nerve stimulation for drug-resistant epilepsy. Soss, J., Heck, C., Murray, D., et al.[2018]

External trigeminal nerve stimulation (eTNS) is a safe and well-tolerated therapy for patients with drug-resistant epilepsy, as shown in a pilot feasibility study.

The study specifically monitored heart rate and blood pressure responses to eTNS, indicating no significant adverse effects on these vital signs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and long-term safety of external trigeminal nerve stimulation for drug-resistant epilepsy. Pop, J., Murray, D., Markovic, D., et al.[2011]

The external trigeminal nerve stimulator (eTNS) significantly reduces the frequency of migraine attacks and headache days, with an average decrease of 0.67 fewer attacks and 2.28 fewer headache days per month in patients.

eTNS is also effective for acute treatment, showing notable pain reduction within 24 hours after treatment, and it has a good safety profile with no serious adverse events reported in the studies analyzed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of external trigeminal nerve stimulator (e-TNS) on prevention and acute treatment of episodic and chronic migraine: A systematic review. Stanak, M., Wolf, S., Jagoš, H., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Double-Blind, Sham-Controlled, Pilot Study of Trigeminal Nerve Stimulation for Attention-Deficit/Hyperactivity Disorder. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

External trigeminal nerve stimulation for drug resistant epilepsy: A randomized controlled trial. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulation in youth with attention-deficit/hyperactivity disorder. [2019]

4. England pubmed.ncbi.nlm.nih.gov

An audit of external trigeminal nerve stimulation (eTNS) in epilepsy. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A prospective long-term study of external trigeminal nerve stimulation for drug-resistant epilepsy. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Acute and long-term safety of external trigeminal nerve stimulation for drug-resistant epilepsy. [2011]

7. Netherlands pubmed.ncbi.nlm.nih.gov

The impact of external trigeminal nerve stimulator (e-TNS) on prevention and acute treatment of episodic and chronic migraine: A systematic review. [2023]