Vagus Nerve Stimulation for Autism

(VNS Trial)

Recruiting at 1 trial location

Overseen By Eric B London, M.D.

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: New York State Institute for Basic Research

Must be taking: Psychotropic

Must not be taking: Beta blockers, Beta stimulant, Marijuana

Disqualifiers: Implantable device, Neurological disorders, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-12 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how vagus nerve stimulation (VNS), delivered through a small device called a Vagus Nerve Stimulator, affects behavior, thinking, and daily rhythms in people with autism and developmental disabilities. Participants may choose to undergo this non-invasive treatment for 1 to 3 months, depending on their response. The trial seeks individuals aged 12-40 with autism or intellectual and developmental disabilities who are stable on their current medications and can wear monitoring devices like an Apple Watch. As an unphased trial, this study offers a unique opportunity to contribute to understanding VNS's impact on autism and developmental disabilities.

Do I have to stop taking my current medications for the trial?

You need to be on a stable dose of your current psychotropic medication for at least one month before joining the trial and agree not to start new medications or change your existing ones during the study.

What prior data suggests that this vagus nerve stimulation is safe for autism?

Research shows that vagus nerve stimulation (VNS) is generally safe for people, including children with conditions like epilepsy and autism spectrum disorder (ASD). Studies have found that VNS can help reduce seizures and might improve behavior in people with ASD. VNS has been used for many years to treat epilepsy, so its safety is well understood.

Some studies have examined the side effects of VNS. Common ones include changes in voice, coughing, and throat discomfort. These effects are usually mild and tend to lessen over time. Long-term safety studies in different conditions indicate that most side effects can be managed.

This trial's focus on autism is newer, but existing data from other uses of VNS is encouraging in terms of safety. While more research is needed to fully understand its effects on autism, initial findings are promising for those considering this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for autism, which often include behavioral therapies and medications like antipsychotics, Vagus Nerve Stimulation (VNS) offers a novel approach by targeting the vagus nerve directly. This treatment is unique because it involves a device that sends mild electrical pulses to the vagus nerve, potentially influencing brain activity associated with autism symptoms. Researchers are excited about VNS because it could provide a non-pharmaceutical option with the flexibility to adjust the duration and frequency of stimulation based on individual responses, offering a more personalized treatment approach.

What evidence suggests that Vagus Nerve Stimulation is effective for autism?

Research has shown that stimulating the vagus nerve (VNS) might help people with autism. Some studies found that VNS can improve behaviors in individuals with autism, particularly in younger people. VNS also helped those with autism who have epilepsy, suggesting wider benefits. In animal studies, VNS reduced anxiety and aided with fear responses. These findings provide a promising basis for exploring VNS as a treatment for challenges related to autism. Participants in this trial can experience VNS and choose the duration of their participation based on their response, with options for 1, 2, or 3 months of VNS twice per day. ^{2 6 7 8 9}

Who Is on the Research Team?

Helen Yoo, Ph.D.

Principal Investigator

New York State Institute for Basic Research

Are You a Good Fit for This Trial?

This trial is for children and adults with autism or developmental disabilities. Participants will choose to receive daily Vagus Nerve Stimulation (VNS) treatment for 1, 2, or 3 months and attend monthly study visits. Specific eligibility criteria are not provided.

Inclusion Criteria

Agree not to initiate new or change existing medications or behavior intervention

I am aged 12-40 with IDD or ASD and can give my consent or assent.

I can wear an Apple Watch and EEG, and sit for a brain function test.

Exclusion Criteria

Wards of state

Living in a residential program (e.g., group home)

Any condition per the investigators' clinical judgment that precludes participation in the study (e.g., pregnancy)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily VNS treatment for 1, 2, or 3 months, with the option to extend up to 3 months total

4-12 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vagus Nerve Stimulator

Trial Overview The study tests the effects of VNS on behavior, cognition, and biological rhythms in participants with autism and developmental disorders. It aims to identify who might benefit from VNS and observe how it influences a range of symptoms.

How Is the Trial Designed?

Group I: Vagus Nerve Stimulation (VNS) Experimental Treatment 1 Intervention

Single-subject design: ABA, ABBA, or ABBBA This study allows for a flexibility in the duration of research participation depending on one's response. The participant will be able to select one of the three design options (1, 2, or 3 months of VNS twice per day) in consultation with the study staff. That is, after the initial 1-month trial of VNS, the participant may choose to extend the VNS two more times (i.e., 1 or 2 months), for a total of 90 days.

Vagus Nerve Stimulator is already approved in European Union, United States for the following indications:

Approved in European Union as Vagus Nerve Stimulator for:

• Epilepsy
• Depression
• Stroke rehabilitation

Approved in United States as Vagus Nerve Stimulator for:

• Epilepsy
• Treatment-resistant depression
• Stroke rehabilitation
• Cluster headaches

Who Is Running the Clinical Trial?

New York State Institute for Basic Research

Lead Sponsor

Trials

7

Recruited

960+

Rutgers University

Collaborator

Trials

127

Recruited

2,814,000+

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

Published Research Related to This Trial

Vagal nerve stimulation (VNS) has shown to be an effective treatment for drug-resistant epilepsy, with over 80% of patients experiencing a significant reduction in seizures (more than 50% reduction or complete cessation) after 24 months of therapy.

While there are some side effects related to local irritation of the vagal nerve, these are rare and generally do not lead to serious complications, making VNS a safe alternative to neurosurgery for epilepsy management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation in drug-resistant epilepsy. Experience with 23 patients]. Zwoliński, P., Roszkowski, M., Drabik, K., et al.[2015]

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 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) is a safe and well-tolerated treatment for children with intractable epilepsy, showing no cognitive impairment or adverse drug interactions, and its side effects are generally mild and temporary.

VNS not only maintains efficacy over time but also improves seizure control with prolonged use, making it a potentially reversible alternative to more invasive treatments like surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for control of intractable seizures in childhood. Amar, AP., Levy, ML., McComb, JG., et al.[2017]

In a study of 118 patients with refractory epilepsy who underwent vagus nerve stimulation (VNS), there was a significant average reduction in monthly seizure frequency of 55% over a mean follow-up of 33 months, indicating VNS is an effective long-term treatment option.

VNS was found to be safe, with only 15 patients reporting mild stimulation-related side effects, such as hoarseness or gagging, suggesting that it has a favorable safety profile in a large patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for refractory epilepsy: a transatlantic experience. Vonck, K., Thadani, V., Gilbert, K., et al.[2019]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

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 promising treatment for patients with refractory epilepsy, specifically demonstrated in a case of Lennox-Gastaut Syndrome (LGS).

In this patient, VNS led to an improvement in heart rate variability (HRV), suggesting potential benefits beyond seizure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation improves severely impaired heart rate variability in a patient with Lennox-Gastaut-Syndrome. Koenig, SA., Longin, E., Bell, N., et al.[2022]

In a small study of six very young children (average age 20.5 months) who underwent vagus nerve stimulation (VNS) for epilepsy, 83% experienced a significant reduction in seizure frequency, with 33% becoming seizure-free.

No adverse effects or complications were reported from the VNS procedure, suggesting it is a safe option for treating life-threatening epilepsy in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in children less than 5 years old. Blount, JP., Tubbs, RS., Kankirawatana, P., et al.[2018]

In a study of 16 children with epileptic encephalopathies receiving vagal nerve stimulation (VNS), only 27% experienced a significant reduction in seizure frequency, with a median reduction of 17% overall after one year.

While VNS did not lead to significant improvements in seizure frequency, EEG, or adaptive behavior for the group, it did result in better perceived treatment side effects and general behavior, along with notable verbal performance improvements in some children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagal nerve stimulation in epileptic encephalopathies. Parker, AP., Polkey, CE., Binnie, CD., et al.[2022]

In a retrospective study of 62 patients treated with vagus nerve stimulation (VNS) for epilepsy, only 6 patients experienced significant seizure reduction, indicating that while VNS can be beneficial, it may not be effective for the majority of patients.

Contrary to its reputation for low adverse effects, the study found that only 9 patients had no adverse effects, with some experiencing severe and even life-threatening complications, highlighting the need for careful monitoring throughout the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation therapy in epilepsy patients: long-term outcome and adverse effects: a retrospective analysis]. Carius, A., Wintermantel, A.[2022]

In a study of 60 Norwegian children with difficult-to-treat epilepsy, 72% reported positive effects from vagal nerve stimulation (VNS) after an average follow-up of 2.5 years, with 63% experiencing decreased seizure frequency or severity.

The side effects of VNS were generally mild, with 50% of patients reporting minor side effects, indicating that VNS is a relatively safe and effective additional treatment option for children with refractory epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagal nerve stimulation in children with drug-resistant epilepsy]. Bremer, A., Eriksson, AS., Røste, GK., et al.[2015]

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]

Vagus Nerve Stimulation (VNS) was found to be less effective in treating pediatric epilepsy patients with intellectual disability (ID) compared to those without ID, with a significant difference in outcomes (p = 0.028, OR 0.18).

Despite the reduced efficacy, many studies reported improvements in quality of life for children with ID undergoing VNS, and the treatment was generally well tolerated with transient side effects, indicating it may still be a viable option for this challenging population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation in children: A focus on intellectual disability. Sourbron, J., Klinkenberg, S., Kessels, A., et al.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20515333/

Vagus nerve stimulation therapy in patients with autism ... Patients with ASD and intractable epilepsy respond as favorably as all other patients receiving VNS therapy. In addition, they may experience a number of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8924444/

Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic ... These results suggested that the VNS had a positive effect on autistic behaviors, which provided a preliminary clinical basis that VNS may benefit to younger ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0165032725001156

Vagus nerve stimulation rescues impaired fear extinction ... Vagus nerve stimulation (VNS) has an anxiolytic effect in rats and, when coupled with fear extinction training, VNS enhances extinction of fear in healthy rats.

4. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1337101/full

Effects of transcutaneous auricular vagus nerve stimulation ... In this study, we intend to provide a study protocol to examine the therapeutic effects of taVNS in individuals diagnosed with HFA and to investigate the ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586818322082

Neuromodulation of autism spectrum disorders using vagal ... There is some evidence that VNS, when performed for epilepsy, may improve behaviour in people with ASD.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5496407/

Vagus nerve stimulation as a potential adjuvant to behavioral ... Studies using VNS in children with both epilepsy and an autism spectrum disorder have also yielded positive results. VNS reduces seizure ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06258590

Study Details | NCT06258590 | taVNS for Anxiety in ASD This pilot trial will be an open-label investigation of the safety and feasibility of transcutaneous auricular vagus nerve stimulation (taVNS) as a ...

8. jpbs.hapres.com jpbs.hapres.com/SwitchArticles.aspx?cid=1492&direction=right

Vagus Nerve Stimulation as a Treatment for Fear and ... Vagus nerve stimulation therapy in patients with autism spectrum disorder ... Vagus Nerve Stimulation , Side Effects , and Long-Term Safety. J Clin ...

9. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2016.00609/full

Transcutaneous Vagus Nerve Stimulation: A Promising ... tVNS can activate the brain regions associated with Autism Spectrum Disorder (ASD), trigger neuroimmune modulation and produce treatment effects.