Influence of Ear Vagus Nerve Stimulator on Patients With IBS

NCT06321237 | Not Yet Recruiting

• 1 other identifier: TJ-IRB202402130
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Irritable Bowel Syndrome

Keywords

Ear nail stimulator; Gut microbiota; Vagus nerve stimulation

Outcome Measures

Primary Outcomes (4)

• Changes in irritable bowel symptoms

  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

  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

  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

  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

Study Arms (4)

The true-true stimulus group

ACTIVE COMPARATOR

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 true-false stimulus group

EXPERIMENTAL

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 false-true stimulus group

EXPERIMENTAL

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 false-false stimulus group

PLACEBO COMPARATOR

Over the course of the 8-week intervention, the patient used an ear nail stimulator that gave false stimulation

Device: Pseudostimulus

Interventions

Vagus nerve stimulation for 8 weeks DEVICE

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

The true-true stimulus group

Vagus nerve stimulation for the first 4 weeks DEVICE

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

The true-false stimulus group

Vagus nerve stimulation for the last 4 weeks DEVICE

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

The false-true stimulus group

Pseudostimulus DEVICE

The patient is given some electrical stimulation but not vagus nerve stimulation

The false-false stimulus group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 、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

You may not qualify if:

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

Sponsors & Collaborators

• Huaping Xie: lead

Related Publications (25)

• Jumpertz R, Le DS, Turnbaugh PJ, Trinidad C, Bogardus C, Gordon JI, Krakoff J. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr. 2011 Jul;94(1):58-65. doi: 10.3945/ajcn.110.010132. Epub 2011 May 4.

  PMID: 21543530 RESULT

• Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922.

  PMID: 21475195 RESULT

• Goldsmith JR, Sartor RB. The role of diet on intestinal microbiota metabolism: downstream impacts on host immune function and health, and therapeutic implications. J Gastroenterol. 2014 May;49(5):785-98. doi: 10.1007/s00535-014-0953-z. Epub 2014 Mar 21.

  PMID: 24652102 RESULT

• Bonaz B, Sinniger V, Pellissier S. Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation. J Physiol. 2016 Oct 15;594(20):5781-5790. doi: 10.1113/JP271539. Epub 2016 May 1.

  PMID: 27059884 RESULT

• Yu CD, Xu QJ, Chang RB. Vagal sensory neurons and gut-brain signaling. Curr Opin Neurobiol. 2020 Jun;62:133-140. doi: 10.1016/j.conb.2020.03.006. Epub 2020 May 4.

  PMID: 32380360 RESULT

• Johnston GR, Webster NR. Cytokines and the immunomodulatory function of the vagus nerve. Br J Anaesth. 2009 Apr;102(4):453-62. doi: 10.1093/bja/aep037. Epub 2009 Mar 3.

  PMID: 19258380 RESULT

• Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ. The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med. 2003 May-Aug;9(5-8):125-34.

  PMID: 14571320 RESULT

• Matteoli G, Gomez-Pinilla PJ, Nemethova A, Di Giovangiulio M, Cailotto C, van Bree SH, Michel K, Tracey KJ, Schemann M, Boesmans W, Vanden Berghe P, Boeckxstaens GE. A distinct vagal anti-inflammatory pathway modulates intestinal muscularis resident macrophages independent of the spleen. Gut. 2014 Jun;63(6):938-48. doi: 10.1136/gutjnl-2013-304676. Epub 2013 Aug 8.

  PMID: 23929694 RESULT

• Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006 Apr;130(5):1480-91. doi: 10.1053/j.gastro.2005.11.061.

  PMID: 16678561 RESULT

• Wang Y, Zheng F, Liu S, Luo H. Research Progress in Fecal Microbiota Transplantation as Treatment for Irritable Bowel Syndrome. Gastroenterol Res Pract. 2019 Dec 1;2019:9759138. doi: 10.1155/2019/9759138. eCollection 2019.

  PMID: 31885549 RESULT

• Shah K, Ramos-Garcia M, Bhavsar J, Lehrer P. Mind-body treatments of irritable bowel syndrome symptoms: An updated meta-analysis. Behav Res Ther. 2020 May;128:103462. doi: 10.1016/j.brat.2019.103462. Epub 2019 Nov 12.

  PMID: 32229334 RESULT

• Muller A, Franke H, Resch KL, Fryer G. Effectiveness of osteopathic manipulative therapy for managing symptoms of irritable bowel syndrome: a systematic review. J Am Osteopath Assoc. 2014 Jun;114(6):470-9. doi: 10.7556/jaoa.2014.098.

  PMID: 24917634 RESULT

• Ford AC, Harris LA, Lacy BE, Quigley EMM, Moayyedi P. Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. Aliment Pharmacol Ther. 2018 Nov;48(10):1044-1060. doi: 10.1111/apt.15001. Epub 2018 Oct 8.

  PMID: 30294792 RESULT

• Bonaz B, Picq C, Sinniger V, Mayol JF, Clarencon D. Vagus nerve stimulation: from epilepsy to the cholinergic anti-inflammatory pathway. Neurogastroenterol Motil. 2013 Mar;25(3):208-21. doi: 10.1111/nmo.12076. Epub 2013 Jan 29.

  PMID: 23360102 RESULT

• Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000 May 25;405(6785):458-62. doi: 10.1038/35013070.

  PMID: 10839541 RESULT

• Bonaz B, Bazin T, Pellissier S. The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front Neurosci. 2018 Feb 7;12:49. doi: 10.3389/fnins.2018.00049. eCollection 2018.

  PMID: 29467611 RESULT

• Foster JA, Rinaman L, Cryan JF. Stress & the gut-brain axis: Regulation by the microbiome. Neurobiol Stress. 2017 Mar 19;7:124-136. doi: 10.1016/j.ynstr.2017.03.001. eCollection 2017 Dec.

  PMID: 29276734 RESULT

• De Ferrari GM, Crijns HJ, Borggrefe M, Milasinovic G, Smid J, Zabel M, Gavazzi A, Sanzo A, Dennert R, Kuschyk J, Raspopovic S, Klein H, Swedberg K, Schwartz PJ; CardioFit Multicenter Trial Investigators. Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur Heart J. 2011 Apr;32(7):847-55. doi: 10.1093/eurheartj/ehq391. Epub 2010 Oct 28.

  PMID: 21030409 RESULT

• Botha C, Farmer AD, Nilsson M, Brock C, Gavrila AD, Drewes AM, Knowles CH, Aziz Q. Preliminary report: modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity. Gut. 2015 Apr;64(4):611-7. doi: 10.1136/gutjnl-2013-306698. Epub 2014 May 28.

  PMID: 24870622 RESULT

• Ghia JE, Blennerhassett P, Kumar-Ondiveeran H, Verdu EF, Collins SM. The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model. Gastroenterology. 2006 Oct;131(4):1122-30. doi: 10.1053/j.gastro.2006.08.016. Epub 2006 Aug 15.

  PMID: 17030182 RESULT

• Asconape JJ, Moore DD, Zipes DP, Hartman LM, Duffell WH Jr. Bradycardia and asystole with the use of vagus nerve stimulation for the treatment of epilepsy: a rare complication of intraoperative device testing. Epilepsia. 1999 Oct;40(10):1452-4. doi: 10.1111/j.1528-1157.1999.tb02019.x.

  PMID: 10528943 RESULT

• Fahy BG. Intraoperative and perioperative complications with a vagus nerve stimulation device. J Clin Anesth. 2010 May;22(3):213-22. doi: 10.1016/j.jclinane.2009.10.002.

  PMID: 20400010 RESULT

• Lacy BE, Patel NK. Rome Criteria and a Diagnostic Approach to Irritable Bowel Syndrome. J Clin Med. 2017 Oct 26;6(11):99. doi: 10.3390/jcm6110099.

  PMID: 29072609 RESULT

• Wiklund IK, Fullerton S, Hawkey CJ, Jones RH, Longstreth GF, Mayer EA, Peacock RA, Wilson IK, Naesdal J. An irritable bowel syndrome-specific symptom questionnaire: development and validation. Scand J Gastroenterol. 2003 Sep;38(9):947-54. doi: 10.1080/00365520310004209.

  PMID: 14531531 RESULT

• Travers P, Lacy BE, Cangemi DJ. Irritable bowel syndrome - less irritable, or better treatments? Curr Opin Gastroenterol. 2024 Jan 1;40(1):27-33. doi: 10.1097/MOG.0000000000000987. Epub 2023 Oct 19.

  PMID: 38078610 RESULT

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Officials

• ping h Xie

  Tongji Medical College of Huazhong University of Science and Technology

  STUDY CHAIR

• qiang Ding

  Tongji Medical College of Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ping h Xie

CONTACT

86+13437187007; hpxie@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 11, 2024
• First Posted: March 20, 2024
• Study Start: April 1, 2024
• Primary Completion: May 26, 2024
• Study Completion: June 9, 2024
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share