Vagal Nerve Stimulation for Indigestion and Gastroparesis

Overseen By Andrew Bolender, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Illicit drugs, Opioids

Disqualifiers: Gastric surgery, Arrhythmias, Epilepsy, Pregnancy, 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: 3

Duration: 4-6 weeks

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to examine how auricular transcutaneous vagal nerve stimulation (taVNS) affects the brain and stomach in individuals with indigestion and gastroparesis. taVNS stimulates the vagal nerve through the ear to determine its impact on symptoms such as nausea, vomiting, and early satiety. Candidates who have experienced gastroparesis symptoms for at least 12 weeks or have functional dyspepsia may qualify if they have not undergone gastric surgery and can abstain from alcohol and caffeine before study sessions. As an unphased trial, this study provides a unique opportunity to explore new treatment possibilities for managing these symptoms.

Will I have to stop taking my current medications?

The trial requires that your current medical treatment for Functional Dyspepsia or Gastroparesis be stable for at least one month before and during the study, so you should not stop taking your current medications if they are part of your stable treatment plan.

What prior data suggests that this technique is safe for treating indigestion and gastroparesis?

Research has shown that taVNS, a method that gently stimulates a nerve in the ear, is generally safe. Studies have found that side effects are usually mild and resolve quickly. For instance, when used to treat IBS-C (a type of irritable bowel syndrome), taVNS alleviated symptoms like constipation and stomach pain, with no serious safety issues reported.

Another study examined taVNS in healthy individuals and found it influenced stomach movement without causing harm. Overall, based on current safety data, taVNS appears to be a promising and safe non-invasive treatment for stomach problems. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for indigestion and gastroparesis, which often include medications like prokinetics and antiemetics, or dietary changes, taVNS (transcutaneous auricular vagus nerve stimulation) acts on the vagus nerve through a non-invasive electrical stimulation method. This treatment is unique because it targets the vagus nerve directly, which plays a critical role in controlling digestive processes. Researchers are excited about taVNS because it offers a potential new mechanism of action that could provide relief without the side effects associated with medications. Additionally, its non-invasive nature makes it a promising option for patients seeking alternative treatments.

What evidence suggests that taVNS is effective for indigestion and gastroparesis?

Studies have shown that transcutaneous auricular vagal nerve stimulation (taVNS), which participants in this trial may receive, can help with certain stomach issues. One study found that adults with functional dyspepsia felt better after using taVNS for four weeks. Another study demonstrated that taVNS affected stomach movement in healthy individuals, indicating potential benefits for stomach movement problems. Additionally, taVNS has improved symptoms in various gut disorders, suggesting it could aid in conditions like gastroparesis. Overall, these findings indicate that taVNS could be a promising treatment for indigestion and gastroparesis. ^{3 5 6 7 8}

Who Is on the Research Team?

Roberta Sclocco, PhD

Principal Investigator

Spaulding Rehabilitation Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with gastroparesis or functional dyspepsia, diagnosed by specific criteria and tests. Participants must have stable medical treatment for a month prior to and during the study, no history of gastric surgery, arrhythmias, seizures, drug abuse or BMI over 32. They can't be pregnant/nursing or planning pregnancy.

Inclusion Criteria

I can avoid alcohol, nicotine, and caffeine for 24 hours before the study.

My stomach condition treatment has been the same for the last month.

You had a test to see how quickly your stomach empties food, and the results showed that your stomach empties too slowly.

Exclusion Criteria

I have had surgery on my stomach or esophagus.

I have epilepsy or have had seizures before.

My BMI is over 32 or my weight is more than 235 lbs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Testing

Baseline testing including consumption of a liquid meal and fMRI brain and gut imaging sessions

1-2 weeks

Multiple visits (in-person)

Treatment

Active or inactive taVNS delivered to the outer ear at a moderate, non-painful level

4-6 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• taVNS

Trial Overview The trial studies auricular transcutaneous vagal nerve stimulation (taVNS) on brain and stomach in patients with indigestion issues like gastroparesis and functional dyspepsia. It aims to understand how taVNS affects these conditions.

How Is the Trial Designed?

Group I: taVNS Experimental Treatment 1 Intervention

Active or inactive taVNS

taVNS is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Depression
• Obesity

Approved in European Union as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Depression

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Transcutaneous auricular vagus nerve stimulation (TaVNS) effectively normalized gastric dysrhythmias in healthy individuals during a water-load test, indicating its potential as a treatment for gastric symptoms.

The study found that TaVNS at 40 Hz improved heart rate variability and reduced bloating, suggesting it positively influences both parasympathetic and sympathetic nervous system pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. Du, P., Maharjan, A., Calder, S., 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]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improved autonomic nerve function in a rat model of functional dyspepsia, as evidenced by decreased gastric sensitivity and increased vagal activity after 14 days of treatment.

Both taVNS and acupuncture at the ST36 acupoint showed similar effects in enhancing acetylcholine levels and M3R receptor expression in gastric tissue, suggesting that taVNS may effectively regulate gastric function through vagus nerve modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of transcutaneous auricular vagus nerve stimulation on autonomic nervous function in rats with functional dyspepsia]. Hou, LW., Rong, PJ., Li, L., et al.[2021]

Transcutaneous auricular vagus nerve stimulation (aVNS) significantly improved gastric motility and reduced hypersensitivity in a rodent model of functional dyspepsia, indicating its potential as a therapeutic intervention.

The study found that aVNS works through anti-inflammatory mechanisms by normalizing the autonomic function and reducing pro-inflammatory cytokines, suggesting it could be a non-pharmacological alternative for treating functional dyspepsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular Vagus Nerve Stimulation Improves Visceral Hypersensitivity and Gastric Motility and Depression-like Behaviors via Vago-Vagal Pathway in a Rat Model of Functional Dyspepsia. Hou, L., Rong, P., Yang, Y., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improves depression symptoms, as evidenced by reduced scores on the Hamilton Depression Scale in a review of 12 studies involving 838 participants.

taVNS shows comparable response rates to traditional antidepressants and has fewer side effects, suggesting it could be a safe alternative or complementary treatment for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. Tan, C., Qiao, M., Ma, Y., et al.[2023]

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]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly reduces gastric sensitivity and enhances gastric emptying in rats with functional dyspepsia, as shown by improved electromyogram (EMG) readings and increased gastric emptying rates after 14 days of treatment.

The mechanism behind taVNS's effectiveness appears to involve up-regulating acetylcholine (ACh) and nicotinic acetylcholine receptor α7 subunit (α7nAChR) levels while inhibiting the inflammatory NF-κB p65 signaling pathway in the duodenum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transcutaneous auricular vagus nerve stimulation promotes gastric motility by up-rgulating α7nAChR and suppressing NF-κB p65 expression in duodenum in rats with functional dyspepsia]. Han, J., Wei, W., Wang, HC., et al.[2022]

Transcutaneous auricular vagal nerve stimulation (taVNS) effectively altered gastric slow wave activity in pigs, showing potential for managing gastric dysfunctions.

The 10 Hz taVNS protocol normalized slow-wave patterns in 90% of subjects, while the 80 Hz protocol inhibited slow waves in 60%, indicating that different frequencies can have distinct effects on gastric motility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of low-and high-frequency non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) on gastric slow waves evaluated using in vivo high-resolution mapping in porcine. Sukasem, A., Cakmak, YO., Khwaounjoo, P., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37787432/

Transcutaneous Auricular Vagal Nerve Stimulation Is ... Our study firstly showed that 4-week taVNS (both 10 and 25 Hz) was effective and safe for the treatment of adult FD ( clinicaltrials.gov ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X2100125X

A randomized, double-blind trial in healthy individuals We provide evidence that 4-h of taVNS influences gastric motility in healthy human participants for the first time using rtMRI.

3. academic.oup.com academic.oup.com/gastro/article/doi/10.1093/gastro/goaf009/7979382

Efficacy of vagus nerve stimulation in gastrointestinal disorders Non-invasive VNS significantly improved symptoms across all subsets of patients, as measured differently according to disease type, compared ...

4. journals.lww.com journals.lww.com/ajg/fulltext/2025/09000/efficacy_and_safety_of_transcutaneous_auricular.33.aspx

Efficacy and Safety of Transcutaneous Auricular Vagus ... ✓ Transcutaneous auricular vagus nerve stimulation (taVNS) ameliorated constipation-predominant IBS-related symptoms and rectal functions. ✓ taVNS activated ...

5. journals.physiology.org journals.physiology.org/doi/full/10.1152/ajpgi.00426.2020?doi=10.1152/ajpgi.00426.2020

Transcutaneous auricular vagal nerve stimulation improves ... In comparison with sham-ES, acute taVNS improved gastric accommodation (P = 0.008), increased the percentage of normal gastric slow waves (%NSW, fasting: P = ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12398348/

Efficacy and Safety of Transcutaneous Auricular Vagus Nerve ... The study manifested that noninvasive taVNS effectively improved constipation and abdominal pain symptoms in patients with IBS-C. The alleviation of IBS-C ...

7. nature.com nature.com/articles/s41598-022-25864-1

Safety of transcutaneous auricular vagus nerve stimulation ... Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05405842

Study Details | NCT05405842 | Transauricular Vagal Nerve ... The goal of this study is to establish parameters of gastric myoelectrical activity and heart rate variability in healthy human subjects and compare and ...