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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new, non-invasive treatment called external trigeminal nerve stimulation (eTNS) to determine its effectiveness in reducing ADHD symptoms in children. The researchers will compare real eTNS treatment to a placebo-like version (sham) over four weeks. They aim to discover if changes in brain activity can predict the treatment's effectiveness. Children aged 7-12 diagnosed with ADHD and not currently taking any medication affecting the brain may be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in ADHD treatment.

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 prior data suggests that this external trigeminal nerve stimulation is safe for children with ADHD?

Research has shown that external trigeminal nerve stimulation (eTNS) is generally safe for children with ADHD. In a study with 62 children aged 8 to 12, the FDA approved eTNS after finding it safe. Children tolerated the treatment well, with no serious side effects. Some minor issues, such as skin irritation at the device site, were noted but were not serious.

Since eTNS is already approved for children with ADHD, it indicates a good safety record. However, ongoing research continues to further confirm its safety and effectiveness. Overall, eTNS appears to be a low-risk option for managing ADHD symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional ADHD treatments that typically involve stimulant medications like Adderall or Ritalin, eTNS (external Trigeminal Nerve Stimulation) offers a non-invasive, drug-free alternative. eTNS works by sending mild electrical pulses to the trigeminal nerve, which may help regulate attention and behavior by influencing brain activity. Researchers are excited about eTNS because it provides a potential option for those who cannot tolerate or do not respond well to medication, and it could minimize common side effects associated with pharmaceutical treatments. Additionally, the nightly use of eTNS may offer a more consistent and controlled approach to managing ADHD symptoms.

What evidence suggests that eTNS is effective for ADHD?

Research has shown that external trigeminal nerve stimulation (eTNS) can help reduce ADHD symptoms in children. In one study with 62 children, those who received eTNS showed much better symptom improvement compared to those who received a sham treatment. In the current trial, participants will be randomized to receive either active eTNS or sham eTNS for 4 weeks. Another study with the Monarch eTNS device also found a decrease in main ADHD symptoms, demonstrating its potential effectiveness. Additionally, a trial where participants knew they were receiving eTNS showed noticeable improvements after 4 to 8 weeks of use. Overall, these findings suggest that eTNS could be a promising non-invasive option for managing ADHD in children. ^{5 6 7 8 9}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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) 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11059677/

The efficacy of real versus sham external Trigeminal Nerve ... The FDA approval of eTNS was based on data from a proof-of-concept randomised controlled trial (RCT) in 62 children with ADHD between 8–12 years of age, showing ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2773021223000524

The use of external Trigeminal Nerve Stimulation as an ... 2019 found a general efficacy of eTNS treatment with the Monarch eTNS stimulator from NeuroSigma, where children showed a decrease in ADHD core symptoms and an ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05374187

Efficacy of Trigeminal Nerve Stimulation for ADHD This study is a large multisite randomized clinical trial to asses the efficacy of external trigeminal nerve stimulation (TNS), a novel, minimal risk, ...

4. nature.com nature.com/articles/s41380-023-02227-4

Clinical and cognitive effects of external trigeminal nerve ... One open-label trial (N = 21, children/adolescents with ADHD) reported significant improvement at 4 and 8 weeks of nightly eTNS relative to ...

5. molinahealthcare.com molinahealthcare.com/-/media/Molina/PublicWebsite/PDF/Providers/il/Medicaid/Monarch-external-Trigeminal-Nerve-Stimulation_eTNS_System_MCP_392.pdf

Monarch Trigeminal Nerve Stimulation (eTNS) System ... An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulation in youth with attention-deficit/hyperactivity disorder.

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/reviews/DEN180041.pdf

De Novo Summary (DEN180041) Page 1 of 1 FDA identifies ... The table below identifies the risks to health that may be associated with use of a transcutaneous nerve stimulator for Attention Deficit ...

7. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf23/K233293.pdf

January 16, 2024 NeuroSigma, Inc. Blake Wilson Regulatory ... The Monarch external Trigeminal. Nerve Stimulation (eTNS) System is indicated for treatment of pediatric. Attention. Deficit. Hyperactivity ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT07214545

Study Details | NCT07214545 | External Trigeminal Nerve ... The goal of this clinical trial is to learn if external trigeminal nerve stimulation (eTNS) works to treat ADHD symptoms in children on the ...

9. bcbsm.com bcbsm.com/amslibs/content/dam/public/mpr/mprsearch/pdf/2174289.pdf

MEDICAL POLICY - TRANSCUTANEOUS ELECTRICAL ... External trigeminal nerve stimulation (eTNS) for the management of attention deficit hyperactivity disorder is considered investigational (e.g., ...