Auricular Neurostimulation for Children With Cyclic Vomiting Syndrome: A Randomized, Sham Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Cyclic Vomiting Syndrome Burden Index
研究概览
简要总结
Cyclic vomiting syndrome (CVS) is a fairly common disorder characterized by relentless episodes of vomiting followed by return to baseline health.The majority of children with CVS have concurrent severe abdominal pain and migraine-features, causing significant disability during the attacks. There are very few non-drug treatment options for CVS. Many patients are treated with antidepressants that are often ineffective and may cause serious side effects. Emergency room visits and hospitalizations for patients with CVS is extremely high and the syndrome has an immense impact on quality of life. Safe and effective, non-pharmacological therapies for children with CVS are greatly needed.
Nausea, vomiting and gastrointestinal pain is modulated by the vagus nerve, an important regulator of the autonomic nervous system. The vagus communicates signals between the gastrointestinal tract and the central nervous system. Many studies indicate that vagal nerve stimulation is effective for various pain and vomiting conditions. Recent studies show that vagus nerve signaling is impaired in children with CVS. Researchers have demonstrated safety and efficacy of auricular percutaneous electrical nerve field stimulation (PENFS) targeting the vagus nerve in a small study of children with CVS. The aim of the current study is to investigate the effects of non-invasive PENFS on CVS episode frequency, duration and severity compared to a sham device in a randomized clinical trial.
详细描述
Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction characterized by severe, stereotypical and disabling episodes of intense nausea and vomiting, lasting anywhere from 2 hours to 7 days. The disorder is more prevalent than commonly recognized and is estimated to occur in 1.9% of children. The medical costs for the diagnosis and treatment of CVS are immense and quality of life is markedly affected and worse in children with CVS compared to other gut-brain disorders.
About 80% of patients with CVS suffer from concurrent migraine headaches or abdominal migraines during the episodes. Therapies are therefore targeted both towards both nausea and vomiting and aggressive pain control. Therapies are empiric, and response is often variable with numerous patients still requiring Emergency Room visits or hospital admissions. Tricyclic antidepressants are traditionally the most commonly used "off-label" drugs for children with CVS. These drugs may cause serious side effects, and are frequently discontinued due to intolerable adverse effects. Most recent CVS treatment guidelines in fact call for use of these antidepressants only in refractory cases and instead, increased use of non-pharmacological interventions in all children with CVS. Safer and more effective treatments for children with CVS are much needed. Currently, there are no FDA-approved drugs for the treatment of CVS in children.
The mechanisms underlying CVS remain unclear but there is emerging consensus of altered brain-gut neurocircuitry and autonomic nervous system imbalance. Autonomic abnormalities are previously documented in both children and adults with CVS. Researchers have recently demonstrated significantly altered dynamic, cardiac vagal function in children with CVS compared to age and size matched healthy controls, supporting the use of interventions that target vagal signaling.
Interventions targeting the underlying autonomic imbalance such as auricular vagal nerve stimulation are likely targeting the underlying autonomic imbalance via stimulation of the auricular branch of the vagus in the outer ear. The ear is innervated by several cranial nerves including the vagus (CN X) which projects directly to brainstem nausea and vomiting centers. Stress and elevated sympathetic nervous system activity may contribute to initiation of vomiting in CVS patients and therapy via vagal modulation may alter these signals and prevent episodes.
Non-invasive, auricular neurostimulation using the percutaneous electrical nerve field stimulation (PENFS) device has been demonstrated effective for gastrointestinal pain in a randomized, sham controlled clinical trial. More recently, PENFS was demonstrated effective in an open-label, prospective pilot study of 30 children with drug-refractory CVS. There was a significant improvement in both frequency and duration of CVS episodes from baseline (p<0.0001). Notably, a positive effect on quality of life was demonstrated at long-term follow-up after only 6 weeks of therapy. At 6 months follow-up, 80% demonstrated at least 50% improvement in either frequency or duration of episodes with a median response duration of 113 days. Importantly, 100% of these patients were satisfied with the treatment and no serious side effects were reported. Auricular neurostimulation thus modulates autonomic nervous system balance, thereby improving nausea and vomiting presumably by altering vagal signaling with secondary effects of improving quality of life.
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)
盲法说明
Research coordinator
入排标准
- 年龄范围
- 5 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Episodic vomiting that meet criteria for CVS based on the 2025 NASPGHAN guidelines for diagnosis of pediatric CVS
- •English-speaking
- •Lack of other explanation for vomiting
- •Intact external ear that is free of infection or severe dermatological conditions
- •Stable stable vital signs for their respective age
- •No currently implanted electrical device
- •Family able to accurately describe symptoms and number of vomiting episodes
- •At least 2 vomiting episodes during the 6 months prior to enrollment
排除标准
- •Medically complex children or those who take a medication or suffer from another active disease that explain symptoms
- •Children or their parents who have significant developmental delay
- •Participants diagnosed with alternate conditions that explains their symptoms after undergoing medical workup per standard of care
- •Patients with findings of active disease such as intestinal malrotation, peptic ulcer disease, H.pylori gastritis, celiac disease, inflammatory bowel disease, allergic disorders, hydronephrosis, metabolic disorder or any other active chronic condition or medication that may cause of vomiting
- •Patients who are treated with a new drug affecting the central nervous system in the 4 weeks prior to enrollment
- •Pregnancy
- •Severe cardiopulmonary diseases such as chronic obstructive pulmonary disease (COPD) or coronary artery disease
- •Current chronic marijuana use defined as marijuana use > 2 times per week over the last 6 months prior to study enrollment
- •Previously treated with a PENFS device
研究组 & 干预措施
Active Percutaneous Electrical Nerve Field Stimulation (PENFS)
Active PENFS device x 5 consecutive weeks
干预措施: Active percutaneous electrical nerve field stimulation (Device)
Sham Percutaneous Electrical Nerve Field Stimulation (PENFS)
Sham PENFS device x 5 consecutive weeks
干预措施: Sham percutaneous electrical nerve field stimulation (Device)
结局指标
主要结局
Cyclic Vomiting Syndrome Burden Index
时间窗: From enrollment (baseline) to 6 months after end of treatment
A 5-item survey assessing the frequency, duration and severity of CVS attacks with scores ranging from minimum 0 to maximum 25 and higher score indicating worse outcome.
次要结局
- Symptom Response Scale(From enrollment (baseline) to 6 months after end of treatment)
- Pediatric Migraine Disability Assessment (PedMIDAS)(From enrollment (baseline) to 6 months after end of therapy)
研究者
Gila Ginzburg
Assistant Professor of Pediatrics
Medical College of Wisconsin