Vagal Nerve Stimulation for Indigestion and Gastroparesis

Overseen By Andrew Bolender, BA

Age: 18+

Sex: Any

Trial Phase: Phase < 1

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 tests a treatment that sends mild electrical pulses to the outer ear to help people with stomach issues like functional dyspepsia and gastroparesis. The goal is to see if this can improve communication between the brain and stomach and reduce symptoms. Gastric electrical stimulation (GES) has been proposed as an effective treatment option for patients with gastroparesis that does not respond to other treatments.

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.

Is transcutaneous auricular vagus nerve stimulation (taVNS) safe for humans?

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally considered safe for humans, with only mild and temporary side effects like ear pain, headache, and tingling. A large review found no serious adverse events linked to taVNS, making it a safe option for clinical use. ^{1 2 3 4 5}

How is the treatment taVNS different from other treatments for indigestion and gastroparesis?

taVNS (transcutaneous auricular vagus nerve stimulation) is unique because it is a non-invasive treatment that stimulates the vagus nerve through the skin of the ear to help regulate stomach function, unlike other treatments that may involve medication or surgery. ^{1 3 4 6 7}

What data supports the effectiveness of the treatment taVNS for indigestion and gastroparesis?

Research shows that transcutaneous auricular vagus nerve stimulation (taVNS) can help improve stomach function and reduce symptoms in conditions like functional dyspepsia (indigestion). Studies in both humans and animals suggest that taVNS can enhance stomach movement and reduce discomfort, which may be beneficial for indigestion and gastroparesis. ^{1 3 4 6 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) 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 (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) 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 (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) 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 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) 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. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. [2023]

2. China pubmed.ncbi.nlm.nih.gov

[Effects of transcutaneous auricular vagus nerve stimulation on autonomic nervous function in rats with functional dyspepsia]. [2021]

3. China 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]. [2022]

4. 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]

5. Switzerland 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

7. Netherlands 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. [2023]

8. England 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. [2021]