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

Trial Summary

What is the purpose of this trial?

The goal of this flexible single-subject design vagus nerve stimulation (VNS) study is to examine the behavioral, cognitive, and biorhythmic effects of VNS in children and adults with autism and developmental disabilities. The main aims are: * Pilot the creation of a profile for those who will respond to VNS with the long-term goal of designing clinical trials. * Examine the effects of VNS on a broad range of symptoms. Participants will select between 1, 2, or 3 months of daily VNS treatment and complete study visits each month.

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 data supports the effectiveness of the treatment Vagus Nerve Stimulation (VNS) for autism?

There is some evidence that Vagus Nerve Stimulation (VNS), a treatment that involves stimulating a nerve in the neck, may improve behavior in people with autism, especially when used for epilepsy. This improvement seems to happen even if it doesn't change the frequency of seizures or mood, but more research is needed to confirm these effects. ^{1 2 3 4 5}

Is Vagus Nerve Stimulation (VNS) safe for humans?

Vagus Nerve Stimulation (VNS) is generally considered safe for humans, with most side effects being mild and temporary, such as voice changes or coughing. Serious complications are rare, but surgery-related issues like infection can occur with implanted devices. Non-invasive VNS methods improve safety by avoiding surgery. ^{6 7 8 9 10}

How is Vagus Nerve Stimulation treatment different from other treatments for autism?

Vagus Nerve Stimulation (VNS) is unique because it is a non-drug treatment that involves sending electrical impulses to the vagus nerve, which is different from typical medication-based treatments. It has been used successfully in treating epilepsy and may offer a novel approach for autism by potentially influencing brain activity through nerve stimulation. ^{5 11 12 13 14}

Research Team

Helen Yoo, Ph.D.

Principal Investigator

New York State Institute for Basic Research

Eligibility Criteria

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

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.

I have been on a stable dose of my mental health medication for at least one month.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

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) 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]

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 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]

References

1. Scotland pubmed.ncbi.nlm.nih.gov

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

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

Vagal nerve stimulation in epileptic encephalopathies. [2022]

3. Norway pubmed.ncbi.nlm.nih.gov

[Vagal nerve stimulation in children with drug-resistant epilepsy]. [2015]

4. 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]

5. Germany pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in children less than 5 years old. [2018]

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

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

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

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

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

Vagus nerve stimulation for control of intractable seizures in childhood. [2017]

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

Vagus nerve stimulation for refractory epilepsy: a transatlantic experience. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

11. Poland pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation in drug-resistant epilepsy. Experience with 23 patients]. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation in children: A focus on intellectual disability. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation improves severely impaired heart rate variability in a patient with Lennox-Gastaut-Syndrome. [2022]

14. Germany pubmed.ncbi.nlm.nih.gov

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