Transcutaneous Electrical Acustimulation (TEA) for the Treatment of Non-Erosive Gastroesophageal Reflux Disease (NERD)

Transcutaneous Electrical Acustimulation (TEA) for the Treatment of Non-Erosive Gastroesophageal Reflux Disease (NERD): A Multicenter, Randomized, Sham-Controlled Trial

This multicenter study aims to evaluate whether Transcutaneous Electrical Acustimulation (TEA) is effective in treating Non-Erosive Gastroesophageal Reflux Disease (NERD). NERD is a common condition where patients experience symptoms like heartburn and regurgitation, but no visible damage can be seen in the esophagus during an endoscopy. TEA is a non-invasive treatment that uses a small device to deliver mild electrical stimulation through the skin on specific acupoints. This study will compare the effects of real TEA treatment with a sham (inactive) control. Participants will be randomly assigned to one of two groups: active TEA treatment or sham stimulation. Neither the participants nor the researchers evaluating the outcomes will know which treatment is being given. The main outcome is the improvement of reflux symptoms after 4 weeks of treatment. The results of this study may provide a new non-drug option for patients suffering from NERD.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-erosive Reflux Disease (NERD)
• Intervention / Treatment: Device: Transcutaneous Electrical Acustimulation

Detailed Description

Study Design

This is a prospective, multicenter, randomized, double-blind, sham-controlled, parallel-group clinical trial conducted at multiple centers in China. A total of 204 eligible participants with non-erosive gastroesophageal reflux disease (NERD) will be enrolled and randomly assigned in a 1:1 ratio to receive either active transcutaneous electrical acustimulation (TEA) or sham stimulation for 4 weeks. Randomization will be performed centrally using a computer-generated permuted block design (fixed block size of 4), stratified by study site. Due to differences in stimulation location, treatment administrators will be aware of group assignment; however, participants, outcome assessors, and data analysts will remain blinded to treatment allocation. Group labels (Group A / Group B) will be used in the electronic case report form (eCRF) to maintain blinding.

Study Population

Participants will be recruited from gastroenterology clinics. Eligible participants must meet all of the following criteria: age 18-75 years; typical heartburn symptoms for ≥3 months; heartburn on ≥2 days during the run-in diary period; endoscopically confirmed NERD (no esophageal erosions, Los Angeles grade N/M) within 12 months; and willingness to discontinue acid-suppressive therapy during the study. Key exclusion criteria include familiarity with acupuncture points, presence of esophageal structural or mucosal diseases (e.g., Barrett's esophagus, erosive esophagitis LA grade A-D), gastric or duodenal ulcers, functional heartburn or dyspepsia by Rome IV criteria, uncontrolled systemic diseases, implanted electronic devices (e.g., pacemaker), pregnancy, and participation in other interventional trials within the past 3 months.

All enrolled participants will be categorized based on heartburn frequency during the baseline run-in period (electronic diary) into two subgroups: Subgroup A (heartburn ≥4 days/week) and Subgroup B (heartburn 2-3 days/week). This stratification will be used for prespecified subgroup analyses to explore potential differences in treatment effects across symptom frequency populations.

Intervention and Study Procedures

The total study duration is 10 weeks, consisting of a washout period (Week -2 to Week -1), a baseline run-in period (Week -1 to Week 0), a treatment period (Week 0 to Week 4), and a follow-up period (Week 4 to Week 8).

Active TEA Group: Electrical stimulation will be applied unilaterally at the ST36 (Zusanli) acupoint, located on the anterolateral aspect of the leg, about one finger breadth lateral to the anterior crest of the tibia and just below the tibial tuberosity. One electrode will be placed at ST36 and the other 3-5 cm vertically down from ST36. Stimulation parameters are: 25 Hz pulse frequency, 0.5 ms pulse width, 2 seconds on and 3 seconds off. Current amplitude will range from 1 to 9.5 mA and will be gradually adjusted to the maximum level tolerated by the participant. Participants will self-administer TEA for 1 hour twice daily (morning and evening, within a flexible time window from 6:00 AM to 9:00 PM) for 4 consecutive weeks.

Sham TEA Group: Electrodes will be placed unilaterally at the olecranon and 3-5 cm vertically down from the olecranon, an area not associated with known acupoints for gastrointestinal regulation. The same stimulation device and parameters (including visual and auditory signals) will be used, but the electrical output will not exceed the sensory threshold, providing an identical user experience without active therapeutic stimulation.

Assessments and Outcome Measures

Participants will complete daily electronic symptom diaries from Week -1 through Week 4 and at Week 8. Heartburn severity is assessed using a 0-3 scale (0=none; 1=mild, noticed but does not affect activities; 2=moderate, interferes with daily activities; 3=severe, significantly affects daily life or sleep). A heartburn-free day is defined as a day with a heartburn score of 0 and no use of rescue antacids.

Clinic visits will occur at Week 0 (baseline), Week 4 (end of treatment), and Week 4 (end of treatment). At each visit, participants will complete the Gastroesophageal Reflux Disease Questionnaire (GERD-Q) and the GERD-Health Related Quality of Life (GERD-HRQL) questionnaire. The Patient Global Impression of Change (PGI-C) will be assessed at Week 4. Patient Global Impression of Severity (PGI-S) will be assessed at Week 0, Week 4, and Week 8. Rescue medication use will be recorded from Week 0 to Week 4. Treatment acceptability and persistence of efficacy after TEA discontinuation will be evaluated at Week 8. Safety assessments, including adverse event monitoring, will be conducted throughout the study from Week 0 to Week 8.

Sample Size

The primary endpoint is the proportion of 24-hour heartburn-free days during the 4-week treatment period. Based on prior randomized GERD trials and published TEA studies, the expected proportion of heartburn-free days is estimated at 45% in the TEA group and 25% in the sham group (absolute difference 20%). With a two-sided alpha of 0.05 and 80% power, 86 participants per group are required. Allowing for an anticipated dropout rate of approximately 15%, 102 participants per group will be enrolled, for a total sample size of 204 participants.

Statistical Analysis

Primary analyses will follow the intention-to-treat (ITT) principle, including all randomized participants who received at least one treatment session and provided at least one post-baseline assessment. Per-protocol (PP) analysis will be conducted as a sensitivity analysis. The primary outcome (proportion of heartburn-free days) will be compared between groups using the chi-square test, and further analyzed using logistic regression models adjusting for study site and baseline symptom measures. Secondary continuous outcomes measured repeatedly over time will be analyzed using mixed-effects models. In the ITT analysis, missing primary outcome data will be handled using conservative non-responder imputation (missing diary days considered as non-heartburn-free days). All statistical tests will be two-sided with a significance level of 0.05. Secondary outcome analyses will be interpreted as exploratory and will not be adjusted for multiple comparisons.

Prespecified subgroup analyses will be conducted based on baseline heartburn frequency (≥4 days/week vs. 2-3 days/week). An interaction term "group × heartburn frequency subgroup" will be included to test heterogeneity of treatment effect across subgroups (P_interaction < 0.10 considered significant). All subgroup analyses are exploratory and will not serve as evidence for primary conclusions.

Safety Monitoring

Adverse events (AEs) will be collected systematically throughout the treatment and follow-up periods. Expected AEs based on TEA intervention characteristics include local skin reactions (itching, redness, rash, tingling, burning sensation, mild swelling), electrical stimulation-related discomfort (intolerable tingling, involuntary muscle twitching, dizziness, nausea), and device-related issues. Severity will be graded as mild (no effect on daily activities), moderate (affects daily activities, may require intervention), or severe (significantly affects daily life or requires active medical intervention). Serious adverse events (SAEs) will be reported to the principal investigator within 24 hours and to the ethics committee in accordance with regulatory requirements.

Study Period

The total study duration is from April 1, 2026, to March 31, 2028. Patient recruitment and intervention will occur from April 1, 2026, to December 31, 2027. Data management and statistical analysis will be conducted from January 1, 2028, to January 31, 2028. Study report writing will be completed from February 1, 2028, to March 31, 2028.

• Study Type: Interventional
• Enrollment (Estimated): 204
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qiaosu Zhao, MD; Phone Number: +86-158-6720-0749; Email: zhaoqiaosu_2@163.com
• Study Contact Backup: Name: pengyu Huang, PhD; Phone Number: +86-133-7700-1986

Study Locations

• China
  • Zhejiang
    • Ningbo, Zhejiang, China, 315000
      • Ningbo medical center lihuili hospital
      • Contact: Xiaoyan Ruan, MD; Phone Number: +86-574-87018524; Email: lihuiliethics@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-75 years, irrespective of gender
• Typical heartburn symptoms for at least 3 months
• Heartburn on at least 2 days during the run-in diary period
• Endoscopically confirmed NERD (no esophageal erosions, Los Angeles grade N or M) within 12 months
• Willingness and ability to comply with all study procedures and to provide written informed consent

Exclusion Criteria:

• Familiarity with acupuncture points and their functions (e.g., previous acupuncture experience or medical training)
• Any esophageal structural or mucosal disease (e.g., Barrett's esophagus, erosive esophagitis LA grade A-D, eosinophilic esophagitis, esophageal stricture, varices, malignancy, or prior chemical/thermal/radiation injury)
• Presence of gastric or duodenal ulcers
• History of or suspected diagnosis of functional heartburn or functional dyspepsia by Rome IV criteria
• Systemic diseases affecting gastrointestinal motility (e.g., systemic sclerosis, dermatomyositis, systemic lupus erythematosus, amyloidosis), uncontrolled diabetes mellitus (fasting glucose ≥11.1 mmol/L or glycated hemoglobin ≥7.0%), severe cardiovascular disease, significant hepatic or renal dysfunction, or severe psychiatric disorders
• Inability to discontinue prohibited medications (PPIs, P-CABs, H2RAs, prokinetics, or other GERD-directed therapies) except for protocol-defined rescue medication during the study
• Implanted electronic devices (e.g., pacemaker, defibrillator) or other implants susceptible to electrical stimulation
• Local skin disease or severe hypersensitivity at stimulation sites
• Pregnancy, breastfeeding, or planned pregnancy during the study period
• Participation in other interventional clinical trials within the past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ST36 TEA Group; Participants receive active transcutaneous electrical acustimulation (TEA) at the ST36 (Zusanli) acupoint unilaterally.	Device: Transcutaneous Electrical Acustimulation; Transcutaneous electrical acustimulation delivered via a portable stimulator. Stimulation parameters: 25 Hz pulse frequency, 0.5 ms pulse width, 2 seconds on and 3 seconds off. Current amplitude ranges from 1 to 9.5 mA, adjusted to the maximum level tolerated by the participant. Self-administered at home for 1 hour twice daily (morning and evening, within a flexible time window from 6:00 AM to 9:00 PM) for 4 consecutive weeks.
Sham Comparator: Sham TEA Group; Participants receive sham transcutaneous electrical acustimulation (TEA) with electrodes placed unilaterally at the olecranon and 3-5 cm vertically down from the olecranon.	Device: Transcutaneous Electrical Acustimulation; Transcutaneous electrical acustimulation delivered via a portable stimulator. Stimulation parameters: 25 Hz pulse frequency, 0.5 ms pulse width, 2 seconds on and 3 seconds off. Current amplitude ranges from 1 to 9.5 mA, adjusted to the maximum level tolerated by the participant. Self-administered at home for 1 hour twice daily (morning and evening, within a flexible time window from 6:00 AM to 9:00 PM) for 4 consecutive weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Title Proportion of 24-Hour Heartburn-Free Days During the 4-Week Treatment Period	Description Heartburn is defined as a sensation of warmth, burning, or acid-burning discomfort in the substernal or epigastric region. Heartburn severity is assessed using a 0-3 scale: 0=none; 1=mild (noticed but does not affect activities); 2=moderate (interferes with daily activities); 3=severe (significantly affects daily life or sleep). A heartburn-free day is defined as a day meeting both of the following criteria: heartburn score = 0 on that day, and no use of rescue antacids on that day. The proportion of heartburn-free days is calculated as (number of heartburn-free days) / (number of valid observation days) during the 4-week treatment period.	Day 1 to Day 28 (the 4-week treatment period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly Proportion of 24-Hour Heartburn-Free Days During Treatment	The proportion of heartburn-free days (heartburn score = 0 and no rescue antacid use) calculated separately for each week of the 4-week treatment period.	Week 1, Week 2, Week 3, and Week 4 of the treatment period
Title Change from Baseline in GERD-Q Total Score	Description GERD-Q (Gastroesophageal Reflux Disease Questionnaire) is a 6-item patient-reported outcome measure assessing reflux symptoms and their impact. Total score ranges from 0 to 18, with higher scores indicating more severe symptoms.	Baseline (Week 0), Week 4 (end of treatment), and Week 8 (end of follow-up)
Title Change from Baseline in GERD-HRQL Total Score	GERD-HRQL (Gastroesophageal Reflux Disease-Health Related Quality of Life) is a validated instrument measuring GERD-specific quality of life. Total score ranges from 0 to 50, with higher scores indicating worse quality of life.	Baseline (Week 0), Week 4 (end of treatment), and Week 8 (end of follow-up)
Rescue Medication Use	The proportion of participants requiring rescue antacids during the treatment period, measured as the number of days with rescue medication use and the total amount of rescue medication consumed.	During the 4-week treatment period (Week 0 to Week 4)
Persistence of Efficacy After TEA Discontinuation	The proportion of 24-hour heartburn-free days during the last week of the follow-up period, after TEA treatment has been discontinued. Heartburn-free day defined as heartburn score = 0 and no rescue antacid use on that day.	Last week of follow-up period (Week 8)
Overall Safety Profile of TEA	Description Incidence, severity, and relationship of adverse events (AEs) to the intervention. Expected AEs include local skin reactions (itching, redness, rash, swelling), electrical stimulation-related discomfort (tingling, muscle twitching, dizziness, nausea), and device-related issues.	From Week 0 to Week 8 (entire study period)
Patient Global Impression of Change and Treatment Acceptability	The PGI-C (Patient Global Impression of Change) assesses the participant's perceived change in symptoms on a 7-point scale ranging from 1 to 7, with higher scores indicating greater improvement (better outcome). Treatment acceptability is measured by participant-reported willingness to continue TEA or recommend it to others.	Week 4 (PGI-C) and Week 8 (treatment acceptability)

Collaborators and Investigators

• Sponsor: Ningbo Medical Center Lihuili Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): March 15, 2028
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: May 1, 2026
• First Submitted That Met QC Criteria: May 1, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Neuromodulation; Multicenter; NERD; Transcutaneous electrical Acustimulation
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Gastroesophageal Reflux; Non-Erosive Reflux Disease
• Other Study ID Numbers: KY2026SL117-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared because sharing de-identified data related to acupuncture points and electrical stimulation parameters faces challenges in standardization and is subject to local human genetic resource management restrictions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No