Optimization of taVNS Intervention Strategies for Refractory Constipation

A Prospective, Randomized, Controlled Trial Investigating Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) Intervention Strategies and Neurophysiological Mechanisms in Patients With Refractory Constipation

The goal of this clinical trial is to learn whether transcutaneous auricular vagus nerve stimulation (taVNS) works to treat refractory constipation in adults. It will also learn about the safety and tolerability of taVNS. The main questions it aims to answer are:

Does taVNS improve constipation symptoms, as measured by the change in complete spontaneous bowel movements per week (ΔCSBMs/week) from baseline to post-treatment? What medical problems or side effects do participants have when receiving taVNS? Does taVNS reduce the need for rescue laxatives? Researchers will compare active taVNS to sham taVNS to see if taVNS works to treat refractory constipation.

Participants will:

Be randomly assigned (double-blind) to receive active taVNS or sham taVNS for 20 days Receive stimulation twice daily, 30 minutes per session, with a 12-hour interval between sessions Receive stimulation at 30 Hz with 200 μs pulse width, delivered to the left cymba conchae Keep a daily diary of bowel habits and symptoms, including CSBMs, and rescue laxative use (bowel movements occurring within 24 hours after rescue laxative use will not be counted as CSBMs)

Study Overview

• Status: Recruiting
• Conditions: Refractory Constipation
• Intervention / Treatment: Device: transcutaneous auricular vagus nerve stimulation; Device: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhifeng Zhao, Ph.D; Phone Number: +8613519171072; Email: zhaozhifeng@outlook.com

Study Locations

• China
  • Xi'an, China
    • Recruiting
    • Xijing Hospital
    • Contact: Zhifeng Zhao, Ph.D; Phone Number: +8613519171072; Email: zhaozhifeng@outlook.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria (Revised) Diagnosis of Functional Constipation (FC): Meets Rome IV criteria for functional constipation.

Low CSBM frequency during screening: During the 2-week screening/run-in period, has ≤2 complete spontaneous bowel movements (CSBMs) per week, based on daily diary.

Inadequate response to prior therapy: History of ≥3 months of prior constipation treatment (e.g., laxatives and/or prokinetic agents) with inadequate response (persistent constipation symptoms and/or persistently low CSBM frequency) as documented by medical history and/or records.

Age: 18 to 80 years. Ability to comply: Able and willing to comply with study procedures (including stimulation sessions and diary completion).

No concurrent clinical trial participation: Not participating in another interventional clinical trial during the study period.

Informed consent: Provides written informed consent. Exclusion Criteria (Revised) Organic/secondary causes of constipation: Evidence or history of gastrointestinal organic disease (e.g., inflammatory bowel disease, colorectal tumor, congenital megacolon) or other conditions likely to cause secondary constipation, including endocrine/metabolic disorders (e.g., uncontrolled hypothyroidism, uncontrolled diabetes) or neurological disorders (e.g., Parkinson's disease, spinal cord disorders).

Medications causing constipation (unless stable): Current use of medications known to cause constipation (e.g., opioids, anticholinergics) that cannot be discontinued or kept stable during the study, in the investigator's judgment.

Opioid use disorder or chronic opioid use: History of substance abuse or chronic opioid use that may affect bowel function.

Severe psychiatric conditions or safety risk: Current severe psychiatric disorder requiring urgent intervention, or risk of self-harm/suicide as assessed by a qualified clinician.

Contraindications to taVNS or ear stimulation: Significant ear disease or skin lesions/infection at the stimulation site, or other contraindications to the study device/procedure.

Implanted electronic medical devices: Presence of implanted electrical devices (e.g., pacemaker, implantable cardioverter-defibrillator) or other conditions where electrical stimulation is contraindicated.

Pregnancy or lactation: Pregnant or breastfeeding women. Serious comorbidities that may interfere: Severe or unstable medical conditions that could interfere with participation or outcome assessment (e.g., significant cardiovascular disease/arrhythmia, coagulation disorders or regular anticoagulant therapy, severe hepatic/renal impairment, organ failure).

Cognitive/communication impairment: Cognitive impairment, aphasia, or other conditions preventing valid consent or reliable diary completion.

Investigator discretion: Any condition that, in the investigator's opinion, makes the participant unsuitable for the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: taVNS; Participants will receive active transcutaneous auricular vagus nerve stimulation (taVNS) delivered to the left cymba conchae using the study device. Stimulation will be administered twice daily for 20 consecutive days, with two 30-minute sessions per day separated by approximately 12 hours. Stimulation parameters will be 30 Hz with a 200 μs pulse width (single pulse width 200 μs).	Device: transcutaneous auricular vagus nerve stimulation; Participants will receive active transcutaneous auricular vagus nerve stimulation (taVNS) delivered to the left cymba conchae using the study device. Stimulation will be administered twice daily for 20 consecutive days, with two 30-minute sessions per day separated by approximately 12 hours. Stimulation parameters will be 30 Hz with a 200 μs pulse width (single pulse width 200 μs).
Sham Comparator: Sham-tACS; Participants will receive a sham taVNS procedure designed to mimic active stimulation while not providing effective vagal nerve stimulation. Sham sessions will follow the same schedule and duration as the active arm: twice daily for 20 consecutive days, with two 30-minute sessions per day separated by approximately 12 hours. The sham condition will use an identical-appearing device and procedures to maintain blinding.	Device: Placebo; Participants will receive a sham taVNS procedure designed to mimic active stimulation while not providing effective vagal nerve stimulation. Sham sessions will follow the same schedule and duration as the active arm: twice daily for 20 consecutive days, with two 30-minute sessions per day separated by approximately 12 hours. The sham condition will use an identical-appearing device and procedures to maintain blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive Value of Baseline EEG for Treatment Response (Area Under the Curve)	The ability of baseline EEG spectral power (specifically alpha band power) to classify patients as Responders vs. Non-Responders. Responders are defined as patients with an increase of ≥1 CSBM/week. The performance will be assessed using Receiver Operating Characteristic (ROC) analysis.	Baseline EEG predicting clinical outcome at Day 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in weekly frequency of spontaneous bowel movements (SBM)		Baseline and end of treatment (Day 20)
Change in Complete Spontaneous Bowel Movements per Week (ΔCSBMs/week)	Primary efficacy outcome is the change in weekly complete spontaneous bowel movements (CSBMs) from baseline to end of treatment. A CSBM is defined as a spontaneous bowel movement accompanied by a sensation of complete evacuation. Weekly CSBMs will be derived from daily bowel diaries. Bowel movements occurring within 24 hours after use of rescue laxatives will not be counted as CSBMs.	Baseline to end of treatment (Day 20)
Proportion of participants using polyethylene glycol (PEG) as rescue medication		Baseline and end of treatment (Day 20)
Change from baseline in Patient Health Questionnaire-9 (PHQ-9) score		Baseline and Day 20
Change from baseline in Generalized Anxiety Disorder-7 (GAD-7) score		Baseline and end of treatment (Day 20)
Change from baseline in Patient Health Questionnaire-15 (PHQ-15) somatic symptom score		Baseline and end of treatment (Day 20)

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): January 20, 2026
• Study Completion (Estimated): January 20, 2026

Study Registration Dates

• First Submitted: December 23, 2025
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Actual): January 15, 2026

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Constipation
• Other Study ID Numbers: XJLL-KY-20252521-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• IPD Sharing Access Criteria: For more information or to submit a request, please contact zhaozhifeng@outlook.com.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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