A Prospective, Randomized, Controlled Trial Investigating Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) Intervention Strategies and Neurophysiological Mechanisms in Patients With Refractory Constipation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Predictive Value of Baseline EEG for Treatment Response (Area Under the Curve)
研究概览
简要总结
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(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.
排除标准
- •(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.
结局指标
主要结局
Predictive Value of Baseline EEG for Treatment Response (Area Under the Curve)
时间窗: Baseline EEG predicting clinical outcome at Day 20
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.
次要结局
- 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))
- Change from baseline in Patient Health Questionnaire-15 (PHQ-15) somatic symptom score(Baseline and end of treatment (Day 20))
研究者
Zhifeng Zhao, PhD
Principal Investigator
Xijing Hospital of Digestive Diseases