Vagus Nerve Stimulation for Anxiety in Autism

Overseen By Bashar Badran, PhD

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: 3

Duration: 4 weeks

10 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot participate if you are using medications that substantially reduce seizure threshold, like olanzapine, chlorpromazine, or lithium.

What data supports the idea that Vagus Nerve Stimulation for Anxiety in Autism is an effective treatment?

The available research shows that Vagus Nerve Stimulation (VNS) might help reduce anxiety in individuals with autism. One study suggests that VNS, when used for epilepsy, may also improve behavior in people with autism, even if it doesn't change seizure frequency or mood. Another study highlights that VNS could enhance memory and reduce anxiety when paired with exposure to fear-provoking situations. Additionally, Transcutaneous Vagus Nerve Stimulation (tVNS) has shown potential in activating brain regions linked to autism and improving mood, which could help with anxiety. However, more rigorous studies are needed to confirm these findings. ^{1 2 3 4 5}

What safety data exists for vagus nerve stimulation for anxiety in autism?

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally considered safe with mild and transient adverse effects. A systematic review and meta-analysis evaluated 177 studies with 6322 subjects and found no significant difference in the risk of adverse events between active taVNS and controls. The most common adverse effects were ear pain, headache, and tingling, with no severe adverse events linked to taVNS. Overall, taVNS is a safe and feasible option for clinical intervention. ^{1 6 7 8 9}

Is transcutaneous auricular vagus nerve stimulation a promising treatment for anxiety in autism?

Yes, transcutaneous auricular vagus nerve stimulation (tVNS) is considered a promising treatment for anxiety in autism. It has shown potential in regulating mood and improving symptoms related to autism, such as anxiety, by activating certain brain regions and modulating the nervous system. ^{1 3 4 5 10}

What is the purpose of this trial?

Investigators will recruit up to 10 patients with Anxiety comorbid with Autism Spectrum Disorder (ASD) from the outpatient clinics at MUSC. This pilot trial will be an open-label investigation of the safety and feasibility of transcutaneous auricular vagus nerve stimulation (taVNS) as a nonpharmacological wearable intervention used to manage anxiety and other neuropsychiatric symptoms at home, with patients/caretakers self-administering treatments. Each subject will undergo an initial in-person screening and be consented prior to participating in the study. This will be followed by an in-person training session with the subject (and caretaker if applicable), where they will learn how to self-administer taVNS and ask any pertinent questions. Participants will self-administer taVNS at home twice daily for 4 weeks. These treatments will not interfere with other aspects of their mental health care. Our investigators, over the prior 8 years, have demonstrated that taVNS is safe and feasible in the outpatient setting. Furthermore, investigators have recently demonstrated that taVNS is well tolerated and safely self-administered at home with remote monitoring. The investigators hypothesize that taVNS will be safe and feasible to administer at home in this new population. Results from this study may lead to further exploration of taVNS in this unique population.

Eligibility Criteria

This trial is for English-speaking individuals aged 12-17 with Autism Spectrum Disorder (ASD) who also experience anxiety. They must have been previously diagnosed using the ADOS, score above 24 on the SCARED anxiety scale, and have an IQ over 70. Participants need to be able to give their own assent while consent will be provided by a legal guardian.

Inclusion Criteria

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

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

English speaking

Exclusion Criteria

I am able to understand and participate in the consent process.

Pregnancy

I have had a heart attack or an irregular heartbeat.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Training

Participants receive in-person training on how to self-administer taVNS

1 visit

1 visit (in-person)

Treatment

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

4 weeks

Weekly electronic questionnaires

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) at the end of treatment, electronic questionnaires

Treatment Details

Interventions

• Transcutaneous auricular vagus nerve stimulation

Trial Overview The study tests transcutaneous auricular vagus nerve stimulation (taVNS), a non-drug wearable intervention for managing anxiety in ASD patients at home. It involves self-administering taVNS twice daily for four weeks without affecting other mental health treatments.

Participant Groups

Group I: tVNS Experimental Treatment 1 Intervention

All patients will receive at-home Transcutaneous auricular vagus nerve stimulation (taVNS) and assess the impact on multiple behavioral outcomes associated with ASD and anxiety. This is an open-label trial.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Findings from Research

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]

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]

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]

Vagus nerve stimulation (VNS) may serve as a promising additional treatment for anxiety disorders in children with autism spectrum disorder (ASD), especially when combined with exposure-based cognitive behavioral therapies, which currently have high relapse rates.

Preclinical research suggests that VNS can enhance the consolidation of extinction memories and reduce anxiety, indicating its potential effectiveness not only for anxiety but also for related conditions like depression and epilepsy in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation as a Treatment for Fear and Anxiety in Individuals with Autism Spectrum Disorder. Shivaswamy, T., Souza, RR., Engineer, CT., et al.[2022]

Vagus nerve stimulation (VNS) may improve behavioral outcomes in individuals with autism spectrum disorders (ASD), based on a review of 11 studies, including case series and reports.

The potential benefits of VNS for behavior in ASD appear to occur independently of its effects on seizure control and mood, suggesting a unique mechanism of action that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation of autism spectrum disorders using vagal nerve stimulation. van Hoorn, A., Carpenter, T., Oak, K., et al.[2019]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive technique that stimulates the vagus nerve in the outer ear, potentially helping to treat pediatric neurodevelopmental and psychiatric disorders by addressing maladaptive neural plasticity.

Current literature suggests that taVNS may be a promising alternative treatment for conditions like autism spectrum disorder and ADHD, especially for children who do not respond to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic applications of transcutaneous auricular vagus nerve stimulation with potential for application in neurodevelopmental or other pediatric disorders. Zhu, S., Zhang, X., Zhou, M., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and effective neuromodulation therapy for a variety of conditions, including epilepsy, depression, and anxiety, indicating its broad therapeutic potential.

Despite its effectiveness, there is currently no standardization among taVNS devices, and further research is needed to clarify the relationship between stimulation parameters and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Wang, L., Wang, Y., Wang, Y., et al.[2022]

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) 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]

In a pilot study involving 11 patients with treatment-resistant anxiety disorders, vagus nerve stimulation (VNS) was found to be relatively well tolerated and showed evidence of acute and long-term improvement in anxiety symptoms, particularly in patients with obsessive-compulsive disorder (OCD).

Out of the nine patients who completed the study, three showed significant improvement in anxiety ratings during the acute phase, and four years post-implantation, some patients continued to experience sustained improvements, suggesting VNS may be a promising adjunctive treatment for anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders. George, MS., Ward, HE., Ninan, PT., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. Germany pubmed.ncbi.nlm.nih.gov

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

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

Vagus Nerve Stimulation as a Treatment for Fear and Anxiety in Individuals with Autism Spectrum Disorder. [2022]

5. Scotland pubmed.ncbi.nlm.nih.gov

Neuromodulation of autism spectrum disorders using vagal nerve stimulation. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic applications of transcutaneous auricular vagus nerve stimulation with potential for application in neurodevelopmental or other pediatric disorders. [2022]

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

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

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

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

A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders. [2022]