Optimization of taVNS Intervention Strategies for Refractory Constipation

NCT07344402 | Recruiting

• 1 other identifier: XJLL-KY-20252521-2
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

Refractory Constipation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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)

  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)

Study Arms (2)

taVNS

EXPERIMENTAL

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

Sham-tACS

SHAM COMPARATOR

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

Interventions

transcutaneous auricular vagus nerve stimulation DEVICE

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).

taVNS

Placebo DEVICE

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.

Sham-tACS

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xijing Hospital of Digestive Diseases: lead

Study Sites (1)

Xijing Hospital

Xi'an, China

RECRUITING

MeSH Terms

Conditions

Constipation

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Zhifeng Zhao, Ph.D

CONTACT

+8613519171072; zhaozhifeng@outlook.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 23, 2025
• First Posted: January 15, 2026
• Study Start: September 1, 2025
• Primary Completion: January 20, 2026
• Study Completion: January 20, 2026
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• Access Criteria: For more information or to submit a request, please contact zhaozhifeng@outlook.com.

Locations

CN (1)