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

Trial Summary

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 data supports the effectiveness of the treatment Trigeminal Nerve Stimulation for ADHD?

Trigeminal nerve stimulation (TNS) has shown potential benefits for ADHD, with a study indicating a reduction in symptoms similar to some nonstimulant medications. It is a noninvasive treatment recently approved by the FDA for children with ADHD, based on a trial showing its effectiveness. ^{1 2 3 4 5}

Is trigeminal nerve stimulation safe for humans?

Trigeminal nerve stimulation (TNS) is generally considered safe and well tolerated in humans, with studies showing minimal and transient side effects. It has been evaluated for conditions like ADHD and epilepsy, and the research indicates it is safe for both short-term and long-term use. ^{1 2 3 5 6}

How is trigeminal nerve stimulation treatment different from other ADHD treatments?

Trigeminal nerve stimulation (TNS) is unique because it is a non-invasive treatment that uses electrical impulses to stimulate a nerve in the face, offering a minimal-risk alternative to medication. Unlike traditional ADHD drugs, TNS has relatively few side effects and is the only device-based treatment approved for children with ADHD by the FDA. ^{1 2 3 5 7}

What is the purpose of this trial?

This is an open-label trial of trigeminal nerve stimulation (TNS) for children aged 8-12 years with attention deficit hyperactivity disorder (ADHD) putatively due to prenatal alcohol exposure (PAE). TNS has been successful in treating pediatric ADHD generally and it is US Food and Drug Administration (FDA)-cleared for this condition. But this will be the first time it is tried for ADHD specifically associated with PAE. In TNS, a weak electric current is applied to the child's forehead overnight while sleeping to gently stimulate the brain. TNS is administered at home by the parent to the child. TNS is safe and well tolerated. Efficacy of TNS in ADHD is \~50%. The purpose of the present pilot study is to determine the feasibility of TNS for children with PAE and ADHD. Feasibility means safety (any serious side effects?), tolerability (do children comply with TNS? are they comfortable with it?), and a rough idea of efficacy (does TNS seem to work in most kids?) A secondary goal of the study is to get a more precise idea of brain mechanisms of TNS with magnetic resonance imaging (MRI). Families who participate will make three clinic visits: eligibility (4-5 hours), pre-TNS (2-3 hours including MRI), and post-TNS (2-3 hours including MRI). Children will receive TNS, applied by the parent, for 8 hours every night while sleeping for 4 weeks. Four weeks after treatment, families will take part in a telephone follow-up, to see whether any improvements made last.

Research Team

Joseph O'Neill, PhD

Principal Investigator

UCLA Division of Child & Adolescent Psychiatry

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

References

1. 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]

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

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

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

Editorial: Precision Medicine in Neurotherapeutics for Attention-Deficit/Hyperactivity Disorder. [2022]

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

Trigeminal Nerve Stimulation for Attention-Deficit/Hyperactivity Disorder: Cognitive and Electroencephalographic Predictors of Treatment Response. [2022]

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

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

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

Pilot study of trigeminal nerve stimulation (TNS) for epilepsy: a proof-of-concept trial. [2006]

7. England pubmed.ncbi.nlm.nih.gov

Trigeminal nerve stimulation restores hippocampal dopamine deficiency to promote cognitive recovery in traumatic brain injury. [2023]