Influence of Ear Vagus Nerve Stimulator on Patients With IBS

March 17, 2024 updated by: Huaping Xie

Effect of Ear Vagus Nerve Stimulator on Symptom Improvement and Intestinal Microbiome in Patients With Irritable Bowel

Irritable bowel syndrome (IBS) is a very common functional digestive disorder characterized by chronic abdominal pain and altered bowel habits in the absence of biological or structural abnormalities. In the field of IBS, effective drug treatments are very limited, and patients are urgently looking for alternatives, including probiotics, hypnotherapy, osteopathy, dietary changes, and fecal microbiota transplants. In recent years, with the continuous elucidation of vagus nerve mechanisms, IBS patients are increasingly interested in bioelectrical regulation, and these patients are often skeptical of traditional drug treatment and believe that drugs are prone to side effects. For several reasons, vagus nerve stimulation (VNS) may be a promising option for improving IBS symptoms. In this experiment, the portable ear nail stimulator produced by Ruishen Medical can accurately stimulate the ear nail, transdermal stimulation of the ear vagus nerve, and give full play to its therapeutic effect. Therefore, the purpose of this clinical trial is to use ear nail stimulator in patients with IBS to explore whether it has therapeutic effects on patients with IBS. To explore the influence of tVNS therapy on irritable bowel syndrome compared with drug therapy, it is hoped that the use of TVNS therapy can reduce the use of related drugs, or even replace drugs. This study intends to recruit a group of patients with irritable bowel syndrome to use the portable ear nail stimulator, (1) to observe whether the symptoms of irritable bowel syndrome patients are improved; (2) To analyze the changes of intestinal microbes in patients with IBS; (3) Verify whether the level of intestinal inflammation is reduced and discover metabolic markers in the intestine.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The human gut microbiome is one of the most densely populated microbial communities on Earth and contains highly diverse microbial communities that provide metabolic, immune and protective functions and play a critical role in human health. The gastrointestinal microbiota is influenced by a variety of factors, including neurological stress, genetics, host physiology (host age, disease, etc.), and environmental factors such as living conditions and drug use. At the same time, the vagus nerve (VN) is considered a key component of the autonomic nervous system (ANS), which innervates most of the digestive tract and many gastrointestinal organs such as the esophagus, stomach, small intestine, and colon, as well as vital organs such as the liver, pancreas, and gallbladder in the digestive system. The vagus nerve transmits excitement to the corresponding brain region by sensing intestinal stimulation, and regulates the gut and brain bidirectionally through the "gut-brain axis". Recent studies have shown that VN has anti-inflammatory effects. This vagus function is mediated through a variety of pathways, some of which remain controversial. The first is the anti-inflammatory pathway of the hypothalamic-pituitary-adrenal axis, stimulated by the afferent fibers of the vagus nerve, where the adrenal glands release cortisol, which provides an important first innate defense against inflammatory infections and helps restore homeostasis in the body. The second, known as the cholinergic anti-inflammatory pathway, releases acetylcholine (ACh) at the synaptic junction with macrophages through the vagal efferent fibre-mediated synaptic connections of intestinal neurons. Acetylcholine binds to the α-7-nicotinic acetylcholine receptor of macrophages and inhibits the release of tumor necrosis (TNF)α, a pro-inflammatory cytokine. The final pathway is the splenic sympathetic anti-inflammatory pathway, where VN stimulates the splenic sympathetic nerve to release acetylcholine from norepinephrine (norepinephrine) at the distal end. Finally, ACh inhibits the release of TNF-α from splenic macrophages through the α-7-nicotinic ACh receptor. Irritable bowel syndrome (IBS) is a very common functional digestive disorder characterized by chronic abdominal pain and altered bowel habits in the absence of biological or structural abnormalities. In the field of IBS, effective drug treatments are very limited, and patients are urgently looking for alternatives, including probiotics, hypnotherapy, osteopathy, dietary changes, and fecal microbiota transplants. In recent years, with the continuous elucidation of vagus nerve mechanisms, IBS patients are increasingly interested in bioelectrical regulation, and these patients are often skeptical of traditional drug treatment and believe that drugs are prone to side effects. For several reasons, vagus nerve stimulation (VNS) may be a promising option for improving IBS symptoms. Vagus nerve stimulation (VNS) is currently used as a treatment option for many clinical conditions, such as heart failure, migraines, and inflammatory bowel disease. VNS techniques are mainly divided into invasive (surgical implantation) and non-invasive (percutaneous)VNS techniques. Invasive VNS (iVNS) involve implanting a programmable pulse generator device in the chest wall and placing electrodes around the left (typical) cervical vagus nerve. As it stands, iVNS has several potential risks, such as bradycardia and cardiac arrest, and localized infections around the wound. The transcutaneous VNS (tVNS) delivery system relies on the skin distribution of the afferent nerve of the vagus nerve to intervene in the outer ear (the auricular branch of the vagus nerve) or the neck (the cervical branch of the vagus nerve), thereby avoiding the risk of surgical implantation of the VNS delivery device and promoting further research on the application of tVNS. In this experiment, the portable ear nail stimulator produced by Ruishen Medical can accurately stimulate the ear nail, transdermal stimulation of the ear vagus nerve, and give full play to its therapeutic effect. Therefore, the purpose of this clinical trial is to use ear nail stimulator in patients with IBS to explore whether it has therapeutic effects on patients with IBS. To explore the influence of tVNS therapy on irritable bowel syndrome compared with drug therapy, it is hoped that the use of TVNS therapy can reduce the use of related drugs, or even replace drugs. This study intends to recruit a group of patients with IBS to use the portable ear nail stimulator. The purpose of the study is (1) to observe whether the symptoms of IBS patients are improved; (2) To analyze the changes of intestinal microbes in patients with IBS; (3) Verify whether the level of intestinal inflammation is reduced and discover metabolic markers in the intestine. This was a randomized, double-blind study with no placebo group and enrolled 40 patients diagnosed with diarrheal irritable bowel syndrome. The enrolled patients were randomly assigned to tVNS true stimulation (real transcutaneous vagal stimulation) and false stimulation (same instrument but no vagal stimulation) at different times. This study does not require recruitment advertisements, and subjects are recruited on a completely voluntary basis. Possible risks during the experiment are explained to subjects and informed consent is signed after they agree to join the study. The volunteers who agreed to join the experiment were surveyed by questionnaire to obtain their intestinal health and other health conditions, and screened according to the above research object selection criteria and exclusion criteria. The collected samples are named by number, which will not disclose the personal information of the subjects. The identity of the subjects is kept secret throughout the study process, and only the number and disease phenotype are visible. Subjects may withdraw from the study at any time. This study will analyze the composition and structure of the gut microbiota of the subjects, and the subjects can keep abreast of the progress of the testing and analysis and obtain their own relevant data. In this study, the Ruishenan auricular vagus nerve stimulator is used directly without installation. Easy to carry, can be opened at any time stimulation, does not affect daily work and life. Currently approved indications are: adjuvant therapy for sleep disorders, anxiety, loss of appetite, fatigue, and adjuvant therapy for diabetes. In this study, ear nail stimulation with a pulse width of 200μs and a frequency of 30Hz was used for 3 hours a day for 8 weeks to improve the clinical symptoms of patients with irritable bowel syndrome. The experimental plan was to collect stool samples from the recruited patients with diarrheal irritable bowel syndrome, and use the ear conchal stimulator for 3h every day with pulse width of 200μs and frequency of 30Hz. The treatment lasted for 8 weeks [28], and each patient was randomly selected as true or false stimulus every 4 weeks, and a total of 4 groups were generated, namely true-true, true-false, false-true, and false-false (Figure 2). The volunteers' stool samples were collected on days 0, 28 and 56. Stool samples were collected two weeks after treatment. On day 0 and every 7 days thereafter, the patients filled in the questionnaire, and a total of 11 questionnaires were collected.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

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Study Contact

Study Contact

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Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

1、All patients were excluded from colorectal tumors by colonoscopy within two years, and their clinical manifestations were diarrheal irritable bowel syndrome, which met the diagnostic criteria of Rome IV

Exclusion Criteria:

  1. Colonoscopy excludes patients with colorectal tumors within one or two years
  2. Patients with other gastrointestinal disorders
  3. Patients with a history of prior abdominal surgery, cardiovascular disease, or serious illness
  4. In the past month, participants had used drugs that could have affected the study results (e.g., probiotics, prebiotics, antibiotics, laxatives, motility agents).
  5. Patients participating in other clinical studies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: The true-true stimulus group
During the 8-week intervention, the patient used the ear nail stimulator to give true stimulation, that is, the vagus nerve stimulation with a pulse width of 200μs and a frequency of 30Hz
Device: Vagus nerve stimulation for 8 weeks
The vagus nerve at the position of the ear nail was stimulated by an ear nail stimulator with pulse width of 200μs and frequency of 30Hz in patients with IBS for 8 weeks
Experimental: The true-false stimulus group
During the 8-week intervention, the first 4 weeks of the auricular stimulator used by the patient were given true stimulation, that is, vagus nerve stimulation with a pulse width of 200μs and a frequency of 30Hz; The next 4 weeks were given as false stimuli
Device: Vagus nerve stimulation for the first 4 weeks
The vagus nerve at the position of the ear nail was stimulated by an ear nail stimulator with pulse width of 200μs and frequency of 30Hz in patients with IBS for the first 4 weeks
Experimental: The false-true stimulus group
During the 8-week intervention, the first 4 weeks of the patient's ear nail stimulator gave false stimulation; The stimulation given in the last 4 weeks is true stimulation, that is, vagus nerve stimulation with pulse width of 200μs and frequency of 30Hz
Device: Vagus nerve stimulation for the last 4 weeks
The vagus nerve at the position of the ear nail was stimulated by an ear nail stimulator with pulse width of 200μs and frequency of 30Hz in patients with IBS for the last 4 weeks
Placebo Comparator: The false-false stimulus group
Over the course of the 8-week intervention, the patient used an ear nail stimulator that gave false stimulation
Device: Pseudostimulus
The patient is given some electrical stimulation but not vagus nerve stimulation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in irritable bowel symptoms
Time Frame: 90 days
Changes in irritable bowel were evaluated by pain degree, frequency of diarrhea, and degree of abdominal distension. Pain degree refers to the use of psychometric practice to evaluate patients' subjective feelings, which is also considered to be a major factor in the evaluation of health-related poor quality of life (HRQL). We measured the severity of IBS using the Gastrointestinal Symptom Score Scale (GSRS-IBS) for IBS. On the GSRS-IBS scale, a score of 1 to 3 is defined as mild, a score of 4 or 5 is defined as more severe, and a score of 6 or 7 is defined as particularly severe
90 days
Changes in the diversity of intestinal flora
Time Frame: 90 days
The changes of intestinal flora diversity before and after the use of ear nail stimulator were analyzed.Alpha diversity is a combination of species richness and evenness in a designated ecosystem. the Bray-Curtis distance reflects the variability in community composition and structure, with greater distances resulting in greater variability between communities.
90 days
Changes in the relative abundance of species of intestinal flora
Time Frame: 90 days
To analyse the changes of relative abundance of species before and after the use of ear nail stimulator in patients.According to the species abundance table of each species, Krona analysis, relative abundance profile display,relative abundance cluster thermogram display, PCA and PCoA dimension reduction analysis, and Wilcoxon test of different species between groups were carried out.
90 days
Changes in the number of intestinal flora
Time Frame: 90 days
Analyse the changes in the number of fecal flora before and after the use of ear nail stimulator in patients with constipation. In order to demonstrate more visually the changes in flora abundance after administration of resistant starch, statistical analyses were carried out using the number of patients who had a 1.5-fold increase or decrease in intestinal flora abundance before and after administration of resistant starch in all patients
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Huaping Xie

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: ping h Xie, Tongji Medical College of Huazhong University of Science and Technology
  • Principal Investigator: qiang Ding, Tongji Medical College of Huazhong University of Science and Technology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

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Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 26, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 9, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 11, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 20, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 20, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TJ-IRB202402130

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Questionnaires filled out by patients before and after using ear nail stimulator, and metagenomic sequencing results of stool samples

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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