Effect of Transcutaneous Auricular Vagal Nerve Stimulation on Functional Dyspepsia

Effect of Transcutaneous Auricular Vagal Nerve Stimulation on Functional Dyspepsia: a Randomized Controlled Trial

Patients with dyspeptic symptoms vary from 10% to 20% globally. Up to 70% of patients with dyspepsia who undergo endoscopy have unremarkable examination and are diagnosed with functional dyspepsia (FD). Given the lack of information related to its pathophysiology, the treatment is largely empirical and of limited efficacy. Previous small study showed therapeutic potential of transcutaneous auricular vagal nerve stimulation (taVNS) for FD. This study aims to investigate whether taVNS can improve the dyspeptic symptoms of patients with FD.

Study Overview

• Status: Unknown
• Conditions: Functional Dyspepsia
• Intervention / Treatment: Device: taVNS 10; Device: taVNS 25; Device: Control

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yanglin Pan, M.D.; Phone Number: 13991811225; Email: yanglinpan@hotmail.com

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China
      • Recruiting
      • Lanzhou University Second Hospital
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing Hospital of Digestive Diseases
      • Contact: Yanglin Pan, M.D.; Phone Number: 86-29-84771536 13991811225; Email: yanglinpan@hotmail.com
    • Xi'an, Shaanxi, China
      • Recruiting
      • The Second Affiliated Hospital of Xi'an Jiaotong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18-65 years old
2. Patients who met the Rome IV diagnostic criteria of FD
3. Moderate to severe FD (functional dyspepsia symptom diary ≥10)
4. Normal upper endoscopy and abdominal ultrasonography within one year.

Exclusion Criteria:

1. Injury or inflammation on the ear
2. Asthma or COPD not under control
3. History of cardiac pacemaker planting or other medical digital devices
4. History of VNS treatment

5. Patients with local or systemic diseases which may cause dyspeptic symptoms:

   Known active peptic ulcer, cholecystitis, gallstone, gastrointestinal obstruction, gastroparesis, and etc.; Known acute or chronic injury of liver or kidney; Obvious hematological abnormality, or endocrine and metabolic diseases; Known malignancy; Obvious cardiovascular or cerebrovascular diseases (such as coronary heart disease, arrhythmia, cerebral infarction and etc.; Other conditions which may be associated with dyspeptic symptoms (such as NSAIDs associated dyspepsia)

6. Patients with serious mental disorders or tendency to suicide
7. Pregnancy or lactic women
8. Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment group 1; Based on the infection of Hp or not, patients will receive quadruple therapy (amoxicillin, clarithromycin, pantoprazole, and bismuth) or PPI (pantoprazole) plus taVNS (produced by by Xi'an Bashui Health Technology Co., Ltd) at left tragus. Patients were given taVNS thirty minutes twice a day in the morning and the night for four weeks (duty circle: 30s "on" periods and 30s "off" periods; frequency: 10 Hz; current intensity: minimal pain threshold; pulse width: 500 μs).	Device: taVNS 10; Patients were given taVNS (by Xi'an Bashui Health Technology Co., Ltd) thirty minutes twice a day in the morning and the night for four weeks (duty circle: 30s "on" periods and 30s "off" periods; frequency: 10 Hz; current intensity: minimal pain threshold; pulse width: 500 μs)
EXPERIMENTAL: Treatment group 2; Based on the infection of Hp or not, patients will receive quadruple therapy (amoxicillin, clarithromycin, pantoprazole, and bismuth) or PPI (pantoprazole) plus taVNS (produced by by Xi'an Bashui Health Technology Co., Ltd) at left tragus. Patients were given taVNS thirty minutes twice a day in the morning and the night for four weeks (duty circle: 30s "on" periods and 30s "off" periods; frequency: 25 Hz; current intensity: minimal pain threshold; pulse width: 500 μs).	Device: taVNS 25; Patients were given taVNS (by Xi'an Bashui Health Technology Co., Ltd) thirty minutes twice a day in the morning and the night for four weeks (duty circle: 30s "on" periods and 30s "off" periods; frequency: 25 Hz; current intensity: minimal pain threshold; pulse width: 500 μs)
ACTIVE_COMPARATOR: Control group; Based on the infection of Hp or not, patients will receive quadruple therapy (amoxicillin, clarithromycin, pantoprazole, and bismuth) or PPI (pantoprazole) plus taVNS (produced by by Xi'an Bashui Health Technology Co., Ltd) at left earlobe. Patients were given taVNS thirty minutes twice a day in the morning and the night for four weeks (duty circle: 30s "on" periods and 30s "off" periods; frequency: 10 Hz; current intensity: minimal pain threshold; pulse width: 500 μs).	Device: Control; Patients were given taVNS (by Xi'an Bashui Health Technology Co., Ltd) thirty minutes twice a day in the morning and the night for four weeks (duty circle: 30s "on" periods and 30s "off" periods; frequency: 10 Hz; current intensity: minimal pain threshold; pulse width: 500 μs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder rate	The proportion of patients whose Functional Dyspepsia Symptom Diary Total Symptom Scores were reduced ≥5 after four weeks treatment when compared with baseline.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Dyspepsia Symptom Diary (FDSD)	The FDSD consists of 5 cardinal items (burning in the stomach, stomach pain, bloating, postprandial fullness, and early satiety) and 3 supplementary items (nausea, burping/belching rating, and burping/belching bother). Each item can be scored from 0 (no) to 10 (worst). Total Symptom Score includes the 5 cardinal items and ranges from 0 to 50.	4 weeks
Gastrointestinal Symptom Rating Scale (GSRS)	The GSRS contains 15 items. All individual items are scored on a 7-point Likert scale (1 = not at all to 7 = extremely) and are subsequently clustered into five domains (abdominal pain, reflux, indigestion, diarrhea, and constipation); higher scores indicate more severe symptoms.	4 weeks
Adequate relief rate	The proportion of patients who acquire overall symptom relief when compared with baseline	4 weeks
Elimination rate of cardinal symptom	The proportion of patients whose cardinal symptom is completely eliminated when compared with baseline.	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short Form of Nepean Dyspepsia Index (SF-NDI)	The SF-NDI consists of 10 questions regarding the effects of dyspepsia symptoms ("stomach problems") on different aspects of life (tension, interference with daily activities, eating/drinking, knowledge/control, and work/study). Each response can be from 1 (not at all affected) to 5 (extremely affected), or 0 (N/A), for a total summed score out of 50.	4 weeks
Hamilton Anxiety and Depression Scale	Anxiety and depression of patients are assessed by using Hamilton Anxiety and Depression Scale. Hamilton Anxiety Scale consists of 14 items. Each item is scored on a scale from 0 (absent) to 4 (most severe) with a total score range of 0-56. Hamilton Depression Scale consists of 17 items. Individual items scored on 3 point (0 to 2) or 5 point scale (0 to 4); 0=absent, 4=most severe. Total score: 0 to 52.	4 weeks
Adverse event		4 weeks

Collaborators and Investigators

• Sponsor: Air Force Military Medical University, China

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2020
• Primary Completion (ANTICIPATED): December 28, 2021
• Study Completion (ANTICIPATED): March 28, 2022

Study Registration Dates

• First Submitted: December 6, 2020
• First Submitted That Met QC Criteria: December 13, 2020
• First Posted (ACTUAL): December 16, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 16, 2020
• Last Update Submitted That Met QC Criteria: December 13, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Functional Dyspepsia
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia
• Other Study ID Numbers: KY20202087-F-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Other researchers can contact PI to get IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No