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P299. Vagus nerve stimulation in Crohn's disease

B. Bonaz1,2, S. Pellissier2, N. Mathieu1, D. Hoffmann3, C. Trocmé4, M. Baudrant-Boga1, V. Sinniger2, C. Picq2,5, O. David2, L. Vercueil3, C. Dantzer6, J.-L. Cracowski7, D. Clarençon5, 1CHU de Grenoble, Clinique Universitaire d'Hépato-Gastroentérologie, Grenoble, France, 2Grenoble Institute of Neurosciences (GIN, INSERM U836), CHU Grenoble, Grenoble Cedex 09, France, 3Pôle de Neurologie, Département de Neurochirurgie, Grenoble Cedex 09, France, 4Institut de Biologie, CHU Grenoble, Grenoble Cedex 09, France, 5IRBA, Biologie, La Tronche, France, 6Laboratoire Inter-Universitaire de Psychologie (EA4145 UPMF/UDS), Université de Savoie, Chambéry, France, 7Centre d'Investigation Clinique, CHU Grenoble, Grenoble Cedex 09, France

Background

The vagus nerve (VN) has an anti-inflammatory role through the cholinergic anti-inflammatory pathway. VN stimulation (VNS) improves colitis in rats (Auton Neurosci 2011;160:82–9). We performed a pilot study (ClinicalTrials.gov NCT01569503) of VNS in patients with active Crohn's disease (CD).

Methods

Patients with moderate to severe CD were included. Clinical evaluation (CDAI), CRP, fecal calprotectin (FC), ileo-colonoscopy (CDEIS), contrast-enhanced ultrasound (CEUS), heart rate variability (HRV, a marker of the sympatho-vagal balance) were performed before VNS and during the follow-up for one year. An electrode was wrapped around the left VN in the neck, under general anesthesia, tunnelized subcutaneously, and connected to a pulse generator (Cyberonics, Lyon, France) located subcutaneously in the left chest wall. VNS was performed with the following parameters: 0.5 mA, 10 Hz, 30 s ON, 5 min OFF, continuous cycle. In case of aggravation, patients were removed from the study and treated with anti-TNF/immunosuppressants or surgery.

Results

4 patients have been included: 3 men/1 women; mean age: 42.5 years (32–50); Montreal classification (A3L1B2, A2L1B3, A2L2B1, A3L2B1); length of the disease (9.5 years; 0.5–26); smoking (2/4). Two patients were naïve of treatment on inclusion, one was under azathioprine (AZA) and one had stopped AZA 3.5 years before. The mean CDAI at entrance was 335 (320–358), CRP: 78 (8–166), FC: 677 (20–1762), CEUS: active disease, CDEIS: 16 (8–30), vagal hypoactivity on HRV was observed in 3/4 patients and uninterpretable in one. Two patients are currently in clinical remission with mucosal healing (CDEIS: 3–0) with a respective follow-up of 20 and 8 months. The patient in deep remission under AZA+VNS stopped AZA after 14 months of VNS and is in remission after 6 months of follow-up. One patient presented an improvement of CDAI and FC but switched to surgery after 2.5 months of VNS because of a persistent CD activity with an entero-enteric fistula and abscess; the patient agreed to pursue VNS alone post-surgery and had endoscopic healing (i0) at 6 months post-surgery. The last patient switched to Infliximab (IFX) and AZA because of an uncontrolled disease after 3 months of VNS despite a transient improvement. Two patients significantly improved HRV vagal tone after 6 months of VNS but not the third one who switched to IFX+AZA. VNS was well tolerated and no patient withdrew from the study due to complications or side-effects.

Conclusion

The preliminary data of this pilot study show the feasibility of VNS which was well tolerated and efficient in 2 patients currently in deep remission; one patient with a failure of VNS is in deep remission 6 months post-surgery. We are currently pursuing the study.