Vagal Nerve Stimulation for Gastric Motor Functions

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Michael Camilleri, M.D., D.Sc.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Mayo Clinic

Must be taking: Anti-seizure drugs

Must not be taking: Immunosuppressants, beta blockers

Disqualifiers: Substance abuse, Psychiatric hospitalization, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The specific aim of this study is to compare simultaneous assessment of gastric emptying and gastric accommodation in response to the same caloric meal before and three months after activation of left cervical VNS. Our hypothesis is that cervical VNS increases gastric accommodation and accelerates gastric emptying.

Will I have to stop taking my current medications?

The trial excludes patients on immunosuppressants, beta blockers, anticholinergics, and clonidine. If you need to change these medications, you must be stable on the new ones for at least one month before starting the trial.

What data supports the effectiveness of the treatment Vagal Nerve Stimulation for gastric motor functions?

Research shows that vagus nerve stimulation (VNS) can help improve gastric functions by promoting gastric emptying, which is the process of moving food from the stomach to the small intestine. This is achieved by increasing the opening of the pylorus (the valve between the stomach and small intestine), as observed in studies using imaging techniques. ^{1 2 3 4 5}

Is vagal nerve stimulation generally safe for humans?

Vagal nerve stimulation (VNS) is generally considered safe, but it can have side effects. Common issues include voice changes, tingling sensations, cough, headache, and throat pain. Serious problems like infection or heart rhythm changes can occur during surgical implantation, but newer non-invasive methods reduce these risks. ^{1 3 6 7 8}

How does vagal nerve stimulation differ from other treatments for gastric motor functions?

Vagal nerve stimulation (VNS) is unique because it uses electrical impulses to influence the vagus nerve, which helps regulate stomach functions, unlike traditional treatments that rely on medications or dietary changes. This approach can improve gastric emptying by increasing the opening of the pylorus (the valve between the stomach and small intestine), offering a novel option for those whose conditions are not well-managed by existing therapies. ^{1 3 4 5 9}

Research Team

Michael Camilleri, M.D., D.Sc.

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults over 18 with drug-resistant epilepsy and disabling seizures, who are not candidates for resective surgery. Participants must be medically stable apart from epilepsy, able to attend study visits, and use birth control if applicable. Excluded are those recently in other trials or hospitalized for psychiatric conditions, on certain medications like anticoagulants or immunosuppressants, weigh over 350 pounds, can't eat eggs (used in tests), have substance abuse history or vocal cord paralysis.

Inclusion Criteria

I experience seizures that significantly affect my daily life.

I have given my written consent and HIPAA authorization.

I am 18 years old or older.

Exclusion Criteria

You have a history of using alcohol, prescription, or illegal drugs in the past two years.

I cannot stop taking my blood thinners for surgery as advised by my doctor.

I use or will use therapies like short-wave or ultrasound for treatment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgery Assessment

Participants undergo combined gastric emptying/accommodation test prior to VNS implantation

1 day

1 visit (in-person)

Post-surgery Assessment

Participants undergo a second identical gastric emptying/accommodation test approximately 3 months after VNS activation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the post-surgery assessment

4 weeks

Treatment Details

Interventions

• Vagal Nerve Stimulant (Device)

Trial Overview The trial studies the effect of vagal nerve stimulation (VNS) on how the stomach functions after eating a meal. Specifically, it looks at whether activating VNS changes the stomach's ability to hold food and pass it into the intestines. Patients' responses before and three months after VNS activation will be compared using imaging techniques.

Participant Groups

Group I: vagal nerve stimulant Experimental Treatment 1 Intervention

The aim is to measure gastric emptying and gastric accommodation in response to a caloric meal before and 3 months after activation of VNS. Therefore, prior to surgery, subjects will undergo combined gastric emptying/accommodation test. Subsequently, participants will undergo a second identical study approximately 3 months after insertion of the VNS.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

Shashank Priya

University of Minnesota

Chief Executive Officer since 2023

PhD in Materials Engineering from Penn State

Charles Semba

University of Minnesota

Chief Medical Officer since 2021

MD from the University of Minnesota Medical School

Findings from Research

In a study of 15 patients with treatment-resistant depression, vagus nerve stimulation (VNS) significantly reduced depression scores over 12 months, with a mean Beck Depression Inventory score dropping from 37.8 to 24.6, indicating a positive treatment effect.

By the end of the year, 28.6% of patients showed a response to VNS, and 7.1% achieved remission, with side effects like hoarseness and nausea being common but not leading to treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year. Cristancho, P., Cristancho, MA., Baltuch, GH., et al.[2012]

Repeated vagal nerve stimulation (VNS) in rats showed significant antidepressant and anxiolytic effects, comparable to the effects of standard antidepressants desipramine and sertraline, as measured by behavioral tests.

The antidepressant effects of VNS were found to depend on serotonergic nerve activity, while noradrenergic nerves also contributed to its anxiolytic effects, indicating a complex mechanism of action for VNS in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serotonergic and noradrenergic pathways are required for the anxiolytic-like and antidepressant-like behavioral effects of repeated vagal nerve stimulation in rats. Furmaga, H., Shah, A., Frazer, A.[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 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 involving 10 female rabbits implanted with a vagus nerve stimulation (VNS) device, no significant adverse effects on fertility, neonatal health, or teratogenicity were observed, suggesting VNS may be safe during pregnancy.

The findings indicate that VNS does not produce systemic effects like traditional medications, making it a potentially safer option for managing conditions such as epilepsy and depression in pregnant individuals, although further research with larger samples is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of the teratogenicity of vagus nerve stimulation in a rabbit model. Danielsson, I., Lister, L.[2016]

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. England pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation promotes gastric emptying by increasing pyloric opening measured with magnetic resonance imaging. [2019]

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

Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year. [2012]

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

Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study. [2023]

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

Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging. [2021]

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

Serotonergic and noradrenergic pathways are required for the anxiolytic-like and antidepressant-like behavioral effects of repeated vagal nerve stimulation in rats. [2022]

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

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

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

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

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

A pilot study of the teratogenicity of vagus nerve stimulation in a rabbit model. [2016]

9. Germany pubmed.ncbi.nlm.nih.gov

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