The Anti-inflammatory Effect of Vagus Nerve Stimulation (VNS): a New Approach in the Treatment of Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Clinical remission 12 months after initiation of VNS
研究概览
简要总结
The purpose of this study is to determine whether (VNS) Vagus Nerve Stimulation , is effective in the treatment of Crohn's disease.
详细描述
Inflammatory bowel diseases or IBD (Crohn's disease and ulcerative colitis) are chronic inflammatory diseases involving the digestive tract, in particular the small bowel and/or the recto-colon. IBD represent a public health problem in Gastroenterology. The etiopathogeny of IBD is multifactorial involving immunological, genetic, infectious and environmental factors. An overarching hypothesis is that an unbalance of the autonomic nervous system, represented by the sympathetic and parasympathetic nervous system (e.g. the vagus nerve) is part of the mechanisms underlying the pathophysiology of IBD. A dysautonomia has been observed in IBD patients and we have recently demonstrated that this dysautonomia was linked to psychological coping, in particular in Crohn's disease. Classically, the vagus nerve, a mixed nerve, has an anti-inflammatory role through its central afferents which secondarily stimulate the hypothalamic-pituitary adrenal axis. Recent data have shown that the anti-inflammatory properties of the vagus nerve also involve peripheral efferents via an interaction of acetylcholine with nicotinic receptors leading to an inhibition of TNF release by macrophages. Vagus nerve stimulation (VNS) is currently used for the treatment of some forms of epilepsy in Human via a stimulation of vagal afferents. We have recently validated a model of chronic VNS (3h/d for 5 days) in freely moving rats by stimulating vagal efferents and we have studied the anti-inflammatory properties of VNS in an experimental model of colitis in rats. VNS significantly decreased body weight loss due to colitis and had an anti-inflammatory effect by decreasing a multivariate index of inflammation. To date, medical treatment of IBD (e.g. 5-aminosalicylates, corticosteroids, immunosuppressives or biotherapies i.e. anti-TNF) is only suspensive. The aim of our project is to propose another type of anti-inflammatory treatment based on neurostimulation of vagal efferents. For this purpose, we aim to perform a pilot study in 10 patients with moderate to severe Crohn's disease despite a reference treatment (corticosteroids and/or immunosuppressives) using the anti-inflammatory properties of VNS as an alternative to anti-TNF therapy. Central and peripheral effect of VNS will be also evaluated by electroencephalographic and sympatho-vagal (heart rate variability) recordings. The finality, at term, is to use VNS as an alternative to the conventional anti-TNF therapy not devoid of side effects, in particular infectious, with the advantage to use an intrinsic anti-inflammatory (anti-TNF) system and to take cover of problems of adherence to treatment which are frequently observed in the medical treatment of IBD.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •* Patients with CD involving the ileo-colon, diagnosed for at least 3 months prior to screening in flare (220\5mg/l and/or fecal calprotectin \<100µg/l
- •* CDEIS \> 7 (Crohn's disease endoscopic index of severity)
- •* Consenting patient
排除标准
- •Known cardiac pathology
- •VNS contraindication
- •Anoperineal CD only or associated with ileocolic lesion
- •Diagnosis of indeterminate colitis, positive stool culture for enteric pathogens
- •CD Surgery within 3 months before screening
- •Short small intestine (<1m)
- •Koenig syndrome
- •Intra-abdominal abscess
- •Fistula with clinical or radiological abscess evidence
- •Anoperineal CD with or without rectal involvement
- •Ileostomy, colostomy, enteral or parenteral feeding
- •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 recent neoplasia, in the year prior to screening
结局指标
主要结局
Clinical remission 12 months after initiation of VNS
时间窗: 12 months after initiation of VNS
Clinical remission at 12 months : 1. Patient without corticoids or a dose of 20mg without dose adjustment (stable treatment) and without anti-TNF, 2. CDAI \<150 or CDAI has dropped by at least 70 or 100 points (Δ70, Δ100) compared with the baseline CDAI 3. Stable immunosuppressive therapy.
次要结局
- Assessment of VNS effectiveness with biological markers(12 months)
- Evaluation of peripheral effects of VNS on sympatho-vagal balance(6 weeks, 6 months, 12 months)
- VNS tolerance(12 months)
- Clinical remission 6 months after initiation of VNS(6 months after initiation of VNS)
- Endoscopic and ultrasound Assessment of VNS effectiveness(12 months)
- Assessment of the central effects of VNS(At 6 weeks, at 6 months, at 12 months)