Trigeminal Nerve Stimulation for ADHD

(TNS-PAE Trial)

Overseen By Joseph O'Neill, PhD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Disqualifiers: Genetic syndromes, Serious illness, Autism, others

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

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if trigeminal nerve stimulation (TNS) can help children with ADHD linked to prenatal alcohol exposure (PAE). TNS uses a gentle electric current applied to the forehead during sleep and is already approved for general ADHD. The study will assess whether TNS is safe, easy for children to use, and appears effective. Children aged 8-12 with ADHD and PAE who can cooperate with tests and MRIs may be suitable candidates. As an unphased trial, this study offers a unique opportunity to contribute to understanding how TNS can specifically benefit children with ADHD and PAE.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that trigeminal nerve stimulation is safe for children with ADHD due to prenatal alcohol exposure?

Research has shown that trigeminal nerve stimulation (TNS) is safe and well-tolerated for children with ADHD. The FDA has approved TNS for treating ADHD, confirming its safety for this condition. Studies indicate that children handle the treatment well, with minimal risks. The process involves applying a gentle electric current to the child's forehead during sleep, softly stimulating the brain. Previous research has not found any serious side effects, and children usually find the treatment comfortable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Trigeminal Nerve Stimulation is unique because it offers a non-invasive approach to managing ADHD, differing significantly from standard treatments like medication and behavioral therapy. Unlike medications such as stimulants, which can have side effects like insomnia and decreased appetite, this treatment involves gentle nerve stimulation that parents can administer while their child sleeps. This novel method targets the trigeminal nerve, a new mechanism for ADHD management, potentially providing a safer and more comfortable alternative for children and their families. Researchers are excited about its potential to offer effective symptom relief with minimal disruption to daily life.

What evidence suggests that trigeminal nerve stimulation is effective for ADHD associated with prenatal alcohol exposure?

Research has shown that trigeminal nerve stimulation (TNS) can help treat ADHD. In earlier studies, about 52% of participants demonstrated significant improvement. TNS aids attention and hyperactivity by sending a gentle electric current to the forehead during sleep, stimulating the brain. The FDA has approved this treatment for ADHD, and it is considered safe and well-tolerated. This trial will administer TNS to test its effectiveness for ADHD related to prenatal alcohol exposure. ^{1 6 7 8 9}

Who Is on the Research Team?

Joseph O'Neill, PhD

Principal Investigator

UCLA Division of Child & Adolescent Psychiatry

Are You a Good Fit for This Trial?

This trial is for children aged 8-12 with ADHD due to prenatal alcohol exposure. They must be able to visit the clinic three times and have a parent who can apply the TNS device nightly for four weeks. Children should also be comfortable undergoing MRI scans.

Inclusion Criteria

Prenatal alcohol exposure (PAE) >6 drinks/week for >= 2 weeks and/or >= 3 drinks on >= 2 occasions throughout gestation per Health Interview for Women/Health Interview for Adoptive and Foster Parents (HIW/HIAFP)

Full-Scale Intelligence Quotient >70 per the Kaufman Brief Intelligence Test (K-BIT-2)

I have been diagnosed with a condition related to alcohol exposure before birth.

Exclusion Criteria

Other toxic exposure per HIW/HIAFP whose influence clearly surpasses that of alcohol (very rare) per study clinician judgement

Gestation < 34 weeks

I have a genetic condition linked to ADHD symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person, 4-5 hours)

Pre-Treatment

Pre-TNS assessment including MRI

1 week

1 visit (in-person, 2-3 hours including MRI)

Treatment

Participants receive TNS treatment at home for 8 hours every night while sleeping

4 weeks

Post-Treatment

Post-TNS assessment including MRI

1 week

1 visit (in-person, 2-3 hours including MRI)

Follow-up

Telephone follow-up to assess lasting improvements

4 weeks

1 visit (telephone)

What Are the Treatments Tested in This Trial?

Interventions

• Trigeminal Nerve Stimulation

Trial Overview The study tests Trigeminal Nerve Stimulation (TNS), where a weak electric current stimulates the brain overnight, on children with ADHD from prenatal alcohol exposure. It checks if TNS is safe, tolerated, and effective in these specific cases.

How Is the Trial Designed?

Group I: Trigeminal Nerve Stimulation Experimental Treatment 1 Intervention

Each child will receive nightly trigeminal nerve stimulation, administered by the parent at bedtime, for 8 hrs while sleeping overnight, nightly for 4 weeks (28 days)

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

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]

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) 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]

Trigeminal nerve stimulation (TNS) was found to be well tolerated in a pilot study involving seven subjects with epilepsy, indicating a favorable safety profile.

Among the participants who completed at least three months of treatment, 57% experienced a significant reduction of 50% or more in seizure frequency, suggesting preliminary efficacy and warranting further research into TNS for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of trigeminal nerve stimulation (TNS) for epilepsy: a proof-of-concept trial. DeGiorgio, CM., Shewmon, A., Murray, D., et al.[2006]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9714960/

Trigeminal Nerve Stimulation for Attention-Deficit/Hyperactivity ... 52% participants in the active group showed clinically meaningful improvement, as determined by the Clinical Global Impression—Improvement (CGI-I) scale, ...

2. 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, ...

3. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0330986

Trigeminal nerve stimulation (TNS) for children with attention ... Trigeminal nerve stimulation (TNS; [35]) was recently found safe and efficacious for core (inattention, hyperactivity) and executive-function symptoms of ADHD ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X1400388X

An Eight-week, Open-trial, Pilot Feasibility Study of ... This study examined the potential feasibility and utility of trigeminal nerve stimulation (TNS) for attention-deficit/hyperactivity disorder (ADHD) in youth.

5. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-024-05650-1

The efficacy of real versus sham external Trigeminal Nerve ... An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulation in youth with attention-deficit/hyperactivity disorder.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12396707/

Trigeminal nerve stimulation (TNS) for children with ... Trigeminal nerve stimulation (TNS; [35]) was recently found safe and efficacious for core (inattention, hyperactivity) and executive-function symptoms of ADHD ...

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. 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., ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6481187/

Double-Blind, Sham-Controlled, Pilot Study of Trigeminal ... This study demonstrates TNS efficacy for ADHD in a blinded sham-controlled trial, with estimated treatment effect size similar to non-stimulants.