Non-invasive Vagus Nerve Stimulation in the Treatment of Crohn's Disease - A Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Change in Fecal Calprotectin From Baseline to 16 Weeks
研究概览
简要总结
To assess the safety and efficacy of transcutaneous vagal stimulation in adult patients with active Crohn's disease.
详细描述
Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) characterized by chronic inflammation in the digestive tract. The pathogenesis of IBD involves immunological, genetic and environmental factors. Currently there is no cure for Crohn's disease and available medical and surgical treatments are expensive and often associated with significant side effects. Anti-tumor necrosis factor alpha (anti-TNF-α) agents are widely used for treatment of Crohn's disease. Electrical neuromodulation is a new treatment approach of bioelectronic medicine, involving molecular medicine, neuroscience, and bioengineering. Multiple possible mechanisms have been proposed for electrical neuromodulation in GI diseases, including central, autonomic, and/or enteric mechanisms. Vagal tone is significantly blunted in IBD and is associated with high TNF- α levels. Animal and preliminary human studies have demonstrated that electrical vagal nerve stimulation (VNS), including non-invasive vagal stimulation (nVNS), exerts an anti-inflammatory effect by harnessing the cholinergic anti-inflammatory pathway. In healthy humans nVNS has been shown to decrease tumor necrosis factor-α levels. Invasive VNS has been shown to improve inflammation in preliminary studies in patients with Crohn's disease.
Adult patients with active Crohn's disease will be asked to self-administer transcutaneous vagal nerve stimulation three times per day for 16 weeks. Inflammatory laboratory markers will be compared for each patient against their baseline levels to determine if the intervention helps reduce inflammation cause by their Crohn's disease. Questionnaires will be administered to evaluation their symptoms, and quality of life over the 16 week treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Crohn's disease diagnosis for at least 3 months, confirmed by clinical, biochemical, and endoscopic evaluations.
- •Patients with CD involving the small bowel and / or colon with active symptoms with Crohn's Disease Activity Index (CDAI) > 220 despite at least one conventional therapy (corticosteroids and/or immunosuppressives) with a stable dose will be included.
- •Elevated Fecal calprotectin ≥ 200 micro g/g within the past 4 weeks prior to enrollment
- •If on corticosteroids, the dose must be stable and ≤ 20mg/day prednisone or equivalent for at least 14 days before entry into study.
- •If on background immunosuppressive treatment the dose must be stable with the following parameters:
- •56 days (8 weeks) for Immunomodulators (methotrexate, 6-MP, Azathioprine) and small molecules (upadacitinib)
- •112 84 days (16 12 weeks) for biologics (Infliximab, Adalimumab, Vedolizumab, Ustekinumab, another biologic Risankizumab)
- •Clinical laboratory evaluations (including a chemistry panel, complete blood count [CBC], and urinalysis [UA]) within the reference range for the test laboratory, unless a typical consequence of CD or deemed not clinically significant by the Investigator.
- •Colonoscopy within the previous 1 year with no evidence of colonic dysplasia or cancer.
- •Able and willing to give written informed consent and comply with the requirements of the study protocol.
排除标准
- •Expectation to increase corticosteroids and/or immunosuppressive treatment
- •Presence of bowel stricture with pre-stenotic dilatation
- •Presence of intra-abdominal or perirectal abscess
- •Crohn's Disease Activity Index (CDAI) < 220
- •Fistula with clinical or radiological evidence of abscess
- •Perianal CD with or without rectal involvement
- •Ileostomy, colostomy, enteral or parenteral feeding
- •Short gut syndrome.
- •Clinical condition medically or surgically unstable that, at the discretion of the investigator would not be compatible with the patient's participation in the study
- •Any malignant neoplasia, in the year prior to screening ,except for nonmelanoma skin cancer.
- •Active treatment with antibiotics
- •Presence of active intestinal infection or documented infection by stool PCR or culture analysis in the previous 6 weeks
- •Continuous treatment with an anti-cholinergic medication, including over the counter medications.
- •Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.
- •Current tobacco or nicotine user within the past 4 weeks (to limit potential confounding effects of exposure to nicotine)
- •Bowel resection surgery within past 90 days prior to study enrollment and on no conventional IBD therapy, or planned surgery within the course of the study
- •Participation in any other Investigational drug and/or treatment currently or planned during the length of the study
- •Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention
- •Pregnancy or Lactation
- •Comorbid disease with high likelihood of requiring corticosteroid use
- •Inability to comply with study and follow-up procedures
- •Non-English speaking.
- •Known cardiac condition causing or with potential to cause arrhythmia
- •Patients diagnosed with narrowing of the arteries (carotid atherosclerosis)
- •Patients who have had surgery to cut the Vagus nerve in the neck (cervical vagotomy)
- •Patients with clinically significant untreated hypertension, hypotension, bradycardia, or tachycardia.
- •Have a metallic device such as a stent, bone plate or bone screw implanted at or near their neck.
- •Are using another device at the same time (e.g., TENS Unit, muscle stimulator)
结局指标
主要结局
Change in Fecal Calprotectin From Baseline to 16 Weeks
时间窗: Baseline and 16 weeks
This test can identify the level of inflammation in the colon of a person with Crohn's Disease. If a person diagnosed with Crohn's Disease subsequently shows low levels (50 -200 ug/mg) of fecal calprotectin, this means that the inflammation is being controlled, so the treatment regime is working.
次要结局
- Change in Crohn's Disease Activity Index (CDAI) From Baseline to 16 Weeks(Baseline and 16 Weeks)
- Change in Serum Cytokine Levels From Baseline to 16 Weeks(16 Weeks)
- Evaluating Change in HRV From Baseline Until Study Completion.(16 Weeks)
- Change in Insulin Levels After First Stimulation(Baseline Visit)
研究者
Sashidhar V. Sagi
Principal Investigator
Indiana University