Transauricular Vagus Nerve Stimulation for Autism Spectrum Disorder

Overseen By Nicole Cash

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Olanzapine, Chlorpromazine, Lithium

Disqualifiers: Seizure, Epilepsy, Psychosis, Mania, others

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

Compensation: Varies

Number of Visits: 6

Duration: 4 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to explore whether a non-invasive form of ear stimulation called transcutaneous auricular vagus nerve stimulation (taVNS) can manage symptoms in patients with autism spectrum disorder (ASD). Additionally, this study also uses magnetic resonance imaging (MRI) to capture images of participants' brains and apply an image processing method called INSCAPE to track brain state changes during taVNS treatment in ASD. Investigators will recruit up to 16 participants with ASD.

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

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using medications that lower the seizure threshold, like olanzapine, chlorpromazine, or lithium.

What data supports the effectiveness of this treatment for autism spectrum disorder?

Research suggests that stimulating the vagus nerve, which is a nerve that connects the brain to the body, may help with mood and social communication in people with autism. This type of treatment has shown promise in helping with related conditions like epilepsy and depression, which often occur alongside autism. ^{1 2 3 4 5}

Is transauricular vagus nerve stimulation (taVNS) safe for humans?

Transauricular vagus nerve stimulation (taVNS) is generally considered safe, with mild and temporary side effects like ear pain, headache, and tingling. A systematic review found no severe adverse events linked to taVNS, and the risk of side effects was similar to those not receiving the treatment. ^{1 3 6 7 8}

How is transauricular vagus nerve stimulation different from other treatments for autism spectrum disorder?

Transauricular vagus nerve stimulation (taVNS) is unique because it is a non-invasive treatment that targets the vagus nerve through the ear to potentially improve symptoms of autism spectrum disorder (ASD). Unlike traditional treatments, taVNS may help regulate mood and social communication by activating specific brain regions and modulating the neuroimmune system, offering benefits for both core ASD symptoms and related conditions like epilepsy and depression. ^{1 2 4 9 10}

Research Team

Xiaolong Peng

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for English-speaking individuals aged 12-17 with a prior diagnosis of Autism Spectrum Disorder (ASD) confirmed by ADOS. Participants must be able to give their own assent, while consent will be provided by a legal guardian.

Inclusion Criteria

I can agree to participate in the study myself, but my legal guardian will also give consent.

English speaking

Prior diagnosis of ASD using autism diagnostic observation schedule (ADOS)

Exclusion Criteria

I am currently experiencing a severe flare-up of my lung condition or symptoms from COVID.

I or my family have a history of seizures, or I take medication that can lower my seizure threshold.

I have had recent facial or ear pain, or injury to my ear.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Evaluation and Training

Participants receive a baseline behavior evaluation and MRI scans, followed by training on self-administering taVNS

1 week

1 visit (in-person)

Treatment

Participants self-administer taVNS or sham stimulation at home twice daily for 4 weeks

4 weeks

At-home administration

Mid-treatment Evaluation

Participants complete a virtual behavioral evaluation after 2 weeks of treatment

1 day

1 visit (virtual)

Post-treatment Evaluation

Participants undergo post-treatment MRI scanning and behavioral evaluation

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with evaluations at 1 and 4 weeks post-treatment

4 weeks

2 visits (virtual)

Treatment Details

Interventions

• Sham Stimulation
• Transauricular Vagus Nerve Stimulation

Trial Overview The study tests transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive ear stimulation, against sham stimulation to manage ASD symptoms. It includes MRI brain imaging to track changes during the taVNS treatment in participants.

Participant Groups

Group I: Active Vagus Nerve Stimulation Active Control 1 Intervention

This active vagus nerve stimulation uses electrodes on the ear to be administered twice daily, seven days per week, for four weeks at-home.

Group II: Sham Stimulation Placebo Group 1 Intervention

This sham nerve stimulation uses electrodes on the ear to be administered twice daily, seven days per week, for four weeks at-home.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

MUSC COBRE in Neurodevelopment and its Disorders (CNDD) Pilot Projects Program (PPP)

Collaborator

Trials

1

Recruited

20+

Findings from Research

A 10-year-old boy with both autism and epilepsy showed initial temporary improvement in seizure control after receiving vagus nerve stimulation, indicating its potential efficacy for seizure management.

In addition to seizure control, the boy experienced modest improvements in behavior and development, suggesting that vagus nerve stimulation may have positive behavioral side effects independent of its effects on seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autistic spectrum disorder, epilepsy, and vagus nerve stimulation. Hull, MM., Madhavan, D., Zaroff, CM.[2022]

Transcutaneous Vagus Nerve Stimulation (tVNS) shows promise as a treatment for Autism Spectrum Disorder (ASD) by potentially regulating mood and social communication through vagal nerve stimulation.

tVNS may also help manage comorbid conditions associated with ASD, such as epilepsy and depression, by activating brain regions linked to these disorders, although the exact mechanism of action is still being studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagus Nerve Stimulation: A Promising Method for Treatment of Autism Spectrum Disorders. Jin, Y., Kong, J.[2020]

The study demonstrated that remote supervised administration of transcutaneous auricular vagus nerve stimulation (taVNS) at home is feasible for 12 patients with autism spectrum disorder (ASD), achieving an 88.5% completion rate over 132 sessions.

Initial results indicated improvements in anxiety and sleep measures after 2 weeks of treatment, suggesting potential efficacy that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy. Black, B., Hunter, S., Cottrell, H., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) showed promising results in two patients with structural focal epilepsy, leading to seizure freedom in one patient after 4 weeks and significant reduction in seizures for the other after 20 weeks.

Both patients experienced improved quality of life with no significant adverse events reported, suggesting that taVNS could be a safe and effective treatment option for individuals with focal epilepsy and preserved cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation therapy in patients with cognitively preserved structural focal epilepsy: A case series report. Shiraishi, H., Egawa, K., Murakami, K., et al.[2023]

Vagus nerve stimulation (VNS) therapy was found to be effective in improving quality of life (QOL) for patients with both autism spectrum disorder (ASD) and intractable epilepsy, with a notable improvement in mood observed at 12 months post-implantation.

Patients with ASD showed similar responses to VNS therapy as those without ASD, indicating that VNS can be a beneficial treatment option for this population, potentially leading to unique QOL improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation therapy in patients with autism spectrum disorder and intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry. Levy, ML., Levy, KM., Hoff, D., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Vagus nerve stimulation (VNS) is a safe and effective treatment for children with drug-resistant epilepsy (DRE), showing stable seizure control over an average follow-up of nearly 3 years.

In addition to controlling seizures, VNS was associated with significant reductions in autistic behaviors, particularly in language, social skills, and self-help, suggesting potential benefits for children with both DRE and autism spectrum disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic Behaviors in Ten Pediatric Patients With Drug Resistant Epilepsy: An Observational Study. Wang, Z., Yuan, X., Zhang, Q., et al.[2023]

In a study of 24 children undergoing intermittent vagal nerve stimulation over a total of 61 patient years, 15 adverse events were reported, with 13 likely related to the device, indicating a need for careful monitoring during treatment.

Despite the occurrence of adverse events, vagal nerve stimulation was generally well tolerated, and unlike standard drug therapies, these events did not typically require stopping the treatment, although they sometimes led to unexpected surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in children receiving intermittent left vagal nerve stimulation. Murphy, JV., Hornig, GW., Schallert, GS., et al.[2019]

Vagus nerve stimulation (VNS) is a neuromodulation technique that has been used since the 1980s primarily for treating epilepsy, but recent research suggests it may also benefit conditions like major depression, anxiety disorders, and Tourette syndrome.

The study proposes that transcutaneous vagus nerve stimulation (tVNS) could be effectively studied by placing electrodes over the mastoid process, potentially expanding the applications of VNS in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in neuropsychiatry: Targeting anatomy-based stimulation sites. Trevizol, A., Barros, MD., Liquidato, B., et al.[2018]

Auricular transcutaneous vagus nerve stimulation (atVNS) significantly enhances memory persistence in naïve mice, indicating its potential as a cognitive enhancer.

In a mouse model of intellectual disability (Fmr1 knockout), atVNS effectively normalized memory deficits, suggesting it could be a promising intervention for cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular transcutaneous vagus nerve stimulation improves memory persistence in naïve mice and in an intellectual disability mouse model. Vázquez-Oliver, A., Brambilla-Pisoni, C., Domingo-Gainza, M., et al.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Autistic spectrum disorder, epilepsy, and vagus nerve stimulation. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagus Nerve Stimulation: A Promising Method for Treatment of Autism Spectrum Disorders. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation therapy in patients with cognitively preserved structural focal epilepsy: A case series report. [2023]

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

Vagus nerve stimulation therapy in patients with autism spectrum disorder and intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic Behaviors in Ten Pediatric Patients With Drug Resistant Epilepsy: An Observational Study. [2023]

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

Adverse events in children receiving intermittent left vagal nerve stimulation. [2019]

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

Vagus nerve stimulation in neuropsychiatry: Targeting anatomy-based stimulation sites. [2018]

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

Auricular transcutaneous vagus nerve stimulation improves memory persistence in naïve mice and in an intellectual disability mouse model. [2020]