Vagal Nerve Stimulation for Gastric Motor Functions

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Academic

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a device called a Vagal Nerve Stimulant (VNS) affects stomach functions in people with certain conditions. Researchers are investigating whether this device helps the stomach process and accommodate food better for those already using it for depression or epilepsy that doesn't respond to medication. Suitable candidates for this trial have already had a VNS device implanted for drug-resistant depression or epilepsy and are stable in their condition. As an unphased trial, this study offers participants the chance to contribute to innovative research that could enhance treatment options for others.

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 prior data suggests that this vagal nerve stimulation is safe for gastric motor functions?

Research shows that vagal nerve stimulation (VNS) has been safely used for some time, particularly for treating hard-to-treat depression. Many patients have tolerated it well. Studies also suggest it might help with stomach problems by improving how the stomach empties and adapts to food.

While VNS is usually well-tolerated, some people might experience side effects like voice changes, coughing, or throat discomfort. Serious issues are rare. Since VNS is already approved for certain conditions, it has passed safety checks for those uses. However, treatments can affect everyone differently.

Prospective trial participants should discuss any concerns with their doctor, who can provide advice based on personal health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of vagal nerve stimulation (VNS) for gastric motor functions because it offers a novel approach to treating conditions like medication-resistant depression by potentially impacting the digestive system. Unlike typical treatments that might focus on balancing neurotransmitters with medication, VNS targets the vagus nerve, which plays a crucial role in regulating gut movement and accommodating food. This method could provide a dual benefit: addressing depression while also enhancing digestive processes, which could be a game-changer for individuals who haven't found relief through standard treatments.

What evidence suggests that vagal nerve stimulation is effective for gastric motor functions?

Research has shown that stimulating the vagus nerve (VNS) might improve stomach function, particularly in emptying food and stretching to accommodate it. Studies have found that VNS can speed up food passage by relaxing the pyloric sphincter, the valve at the stomach's exit. In animal studies, VNS resulted in quicker stomach emptying, suggesting similar effects in humans. This trial will examine the effects of VNS on gastric motor functions, specifically measuring gastric emptying and accommodation in participants treated with VNS for medication-resistant depression. Early results suggest VNS might enhance the stomach's ability to handle food, but further research is needed for confirmation. ^{1 4 5 6 7}

Who Is on the Research Team?

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

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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.

Aside from epilepsy, I am in stable health.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Vagal Nerve Stimulant

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.

How Is the Trial Designed?

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 in participants who have received insertion of the VNS for the treatment of medication - resistant depression.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

Vagus nerve stimulation (VNS) significantly accelerates gastric emptying in rats, with 40.7% of a meal emptied compared to 29.1% with sham treatment, indicating its potential efficacy for gastric disorders.

VNS also enhances pyloric sphincter relaxation and increases antral contraction amplitude and peristaltic velocity, suggesting that it could be a promising electroceutical therapy for managing gastric emptying disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation promotes gastric emptying by increasing pyloric opening measured with magnetic resonance imaging. Lu, KH., Cao, J., Oleson, S., et al.[2019]

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]

Transcutaneous auricular vagal nerve stimulation (taVNS) significantly improved symptoms in adult patients with functional dyspepsia, with response rates of 81.2% for the 10 Hz group and 75.9% for the 25 Hz group compared to only 47% in the sham group after 4 weeks of treatment.

Both frequencies of taVNS (10 Hz and 25 Hz) were equally effective, and the benefits lasted for at least 12 weeks post-treatment, with mild adverse events reported in only 1-3% of participants, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study. Shi, X., Zhao, L., Luo, H., et al.[2023]

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]

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]

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 involving anesthetized rats, vagus nerve stimulation (VNS) was shown to selectively activate afferent pathways, which significantly increased antral motility, suggesting its potential for enhancing gastric function.

Conversely, when VNS primarily activated efferent pathways, it led to a decrease in antral motility as the stimulus intensity increased, indicating that the choice of VNS parameters can greatly influence gastric motility outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging. Lu, KH., Cao, J., Phillips, R., et al.[2021]

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]

Citations

1.

mayo.edu

mayo.edu/research/clinical-trials/cls-20558885

Effect of Vagal Nerve Stimulation on Gastric Motor Functions

The specific aim of this study is to compare simultaneous assessment of gastric emptying and gastric accommodation in response to the same ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6160317/

Vagus Nerve Stimulation Promotes Gastric Emptying by ...

MRI in rats shows that vagus nerve stimulation significantly accelerated gastric emptying by promoting the relaxation of pyloric sphincter.

3.

trialx.com

trialx.com/clinical-trials/listings/298905/effect-of-vagal-nerve-stimulation-on-gastric-motor-functions/

Effect of Vagal Nerve Stimulation on Gastric Motor Functions

Our hypothesis is that cervical VNS increases gastric accommodation and accelerates gastric emptying compared to a bank of healthy control data.

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1094715925000030

Effect and Mechanism of Vagal Nerve Stimulation on ...

VNS was conducted over six sessions to optimize its efficacy on CRD-induced gastric dysrhythmia: control, CRD, and CRD with four different sets of parameters ...

5.

withpower.com

withpower.com/trial/phase-epilepsy-8-2023-e2fe0

Vagal Nerve Stimulation for Gastric Motor Functions

The specific aim of this study is to compare simultaneous assessment of gastric emptying and gastric accommodation in response to a caloric meal In patients ...

6.

centerwatch.com

centerwatch.com/clinical-trials/listings/NCT06038929/effect-of-vagal-nerve-stimulation-on-gastric-motor-functions

Effect of Vagal Nerve Stimulation on Gastric Motor Functions

Our hypothesis is that cervical VNS increases gastric accommodation and accelerates gastric emptying compared to a bank of healthy control data.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8887908/

TENS improves functional dyspepsia by enhancing vagal activity

The proposed method of transcutaneous auricular vagal nerve stimulation improves symptoms of both dyspepsia and depression/anxiety, and gastric functions ( ...