- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01569503
Vagus Nerve Stimulation a New Approach in the Treatment of Crohn's Disease (VNS)
May 2, 2018 updated by: University Hospital, Grenoble
The Anti-inflammatory Effect of Vagus Nerve Stimulation (VNS): a New Approach in the Treatment of Crohn's Disease
The purpose of this study is to determine whether (VNS) Vagus Nerve Stimulation , is effective in the treatment of Crohn's disease.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
9
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Isere
-
Grenoble, Isere, France, 38043
- Grenoble University Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients with CD involving the ileo-colon, diagnosed for at least 3 months prior to screening in flare (220<CDAI<450) of their disease despite a treatment reference (corticosteroids and/or immunosuppressives) with a stable dose will be included
- CRP>5mg/l and/or fecal calprotectin <100µg/l
- CDEIS > 7 (Crohn's disease endoscopic index of severity)
- Consenting patient
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: VSN
VNS therapy
|
VNS therapy consists of an implanted pacemaker-like device that delivers mild, intermittently pulsed signals to the patient's left vagus nerve.
Roughly the size of a small pocket-watch and weighing less than one ounce, the pulse generator is implanted in the patient's left chest area.
A thin thread-like wire, attached to the generator, runs under the skin to the left vagus nerve in the neck
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical remission 12 months after initiation of VNS
Time Frame: 12 months after initiation of VNS
|
Clinical remission at 12 months :
|
12 months after initiation of VNS
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical remission 6 months after initiation of VNS
Time Frame: 6 months after initiation of VNS
|
Clinical remission at 6 months :
|
6 months after initiation of VNS
|
VNS tolerance
Time Frame: 12 months
|
Description and frequency of adverse events
|
12 months
|
Assessment of VNS effectiveness with biological markers
Time Frame: 12 months
|
Assessment of VNS effectiveness with biological markers of the pro-and anti-inflammatory status
|
12 months
|
Endoscopic and ultrasound Assessment of VNS effectiveness
Time Frame: 12 months
|
Endoscopy : CDEIS (Crohn's Disease Endoscopic Index of Severity) Ultrasound : score Migaleddu V. and al, 2009
|
12 months
|
Assessment of the central effects of VNS
Time Frame: At 6 weeks, at 6 months, at 12 months
|
Evolution of :
|
At 6 weeks, at 6 months, at 12 months
|
Evaluation of peripheral effects of VNS on sympatho-vagal balance
Time Frame: 6 weeks, 6 months, 12 months
|
Evolution of cardiac variability markers using time and frequency analysis of electrocardiogram :
|
6 weeks, 6 months, 12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Bruno BONAZ, MD, PHD, Grenoble university hsopital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000 May 25;405(6785):458-62. doi: 10.1038/35013070.
- Meregnani J, Clarencon D, Vivier M, Peinnequin A, Mouret C, Sinniger V, Picq C, Job A, Canini F, Jacquier-Sarlin M, Bonaz B. Anti-inflammatory effect of vagus nerve stimulation in a rat model of inflammatory bowel disease. Auton Neurosci. 2011 Feb 24;160(1-2):82-9. doi: 10.1016/j.autneu.2010.10.007. Epub 2010 Nov 11.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2012
Primary Completion (Actual)
March 30, 2017
Study Completion (Actual)
May 30, 2017
Study Registration Dates
First Submitted
March 30, 2012
First Submitted That Met QC Criteria
April 2, 2012
First Posted (Estimate)
April 3, 2012
Study Record Updates
Last Update Posted (Actual)
May 3, 2018
Last Update Submitted That Met QC Criteria
May 2, 2018
Last Verified
August 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- DCIC11/12
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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