Valérie Sinniger1,2, Sonia Pellissier3, Florence Fauvelle1,4, Candice Trocmé5, Dominique Hoffmann6, Laurent Vercueil1, Jean-Luc Cracowski7, Olivier David1, Bruno Bonaz1,2. 1. Inserm, U1216, Grenoble Institute Neurosciences, University of Grenoble Alpes, Grenoble, France. 2. Division of Hepato-Gastroenterology, CHU Grenoble Alpes, Grenoble, France. 3. University of Grenoble Alpes, University of Savoie Mont Blanc and LIP/PC2S, Grenoble, France. 4. INSERM, US17, MRI facility IRMaGe, University of Grenoble Alpes, Grenoble, France. 5. BEP Laboratory Building, University of Grenoble Alpes Hospital, Grenoble, France. 6. Neurosurgery Department, Grenoble Alpes Hospital, University of Grenoble Alpes Hospital, Grenoble, France. 7. INSERM CIC1406, University of Grenoble Alpes Hospital, Grenoble, France.
Abstract
BACKGROUND: The vagus nerve has anti-inflammatory properties. We aimed to investigate vagus nerve stimulation (VNS) as a new therapeutic strategy targeting an intrinsic anti-inflammatory pathway in a pilot study in Crohn's disease patients. The main objectives addressed the questions of long-term safety, tolerability, and anti-inflammatory effects of this therapy. This study is the continuation of previous reported findings at 6 months. METHODS:Nine patients with moderate active disease underwent VNS. An electrode wrapped around the left cervical vagus nerve was continuously stimulated over 1 year. Clinical, biological, endoscopic parameters, cytokines (plasma, gut), and mucosal metabolites were followed-up. KEY RESULTS: After 1 year of VNS, five patients were in clinical remission and six in endoscopic remission. C-reactive protein (CRP) and fecal calprotectin decreased in six and five patients, respectively. Seven patients restored their vagal tone and decreased their digestive pain score. The patients' cytokinergic profile evolved toward a more "healthy profile": Interleukins 6, 23, 12, tumor necrosis factor α, and transforming growth factorβ1 were the most impacted cytokines. Correlations were observed between CRP and tumor necrosis factor α, and some gut mucosa metabolites as taurine, lactate, alanine, and beta-hydroxybutyrate. VNS was well tolerated. CONCLUSION & INFERENCES: Vagus nerve stimulation appears as an innovative and well-tolerated treatment in moderate Crohn's disease. After 12 months, VNS has restored a homeostatic vagal tone and reduced the inflammatory state of the patients. VNS has probably a global modulatory effect on the immune system along with gut metabolic regulations. This pilot study needs replication in a larger randomized double-blinded control study.
RCT Entities:
BACKGROUND: The vagus nerve has anti-inflammatory properties. We aimed to investigate vagus nerve stimulation (VNS) as a new therapeutic strategy targeting an intrinsic anti-inflammatory pathway in a pilot study in Crohn's diseasepatients. The main objectives addressed the questions of long-term safety, tolerability, and anti-inflammatory effects of this therapy. This study is the continuation of previous reported findings at 6 months. METHODS: Nine patients with moderate active disease underwent VNS. An electrode wrapped around the left cervical vagus nerve was continuously stimulated over 1 year. Clinical, biological, endoscopic parameters, cytokines (plasma, gut), and mucosal metabolites were followed-up. KEY RESULTS: After 1 year of VNS, five patients were in clinical remission and six in endoscopic remission. C-reactive protein (CRP) and fecal calprotectin decreased in six and five patients, respectively. Seven patients restored their vagal tone and decreased their digestive pain score. The patients' cytokinergic profile evolved toward a more "healthy profile": Interleukins 6, 23, 12, tumor necrosis factor α, and transforming growth factorβ1 were the most impacted cytokines. Correlations were observed between CRP and tumor necrosis factor α, and some gut mucosa metabolites as taurine, lactate, alanine, and beta-hydroxybutyrate. VNS was well tolerated. CONCLUSION & INFERENCES: Vagus nerve stimulation appears as an innovative and well-tolerated treatment in moderate Crohn's disease. After 12 months, VNS has restored a homeostatic vagal tone and reduced the inflammatory state of the patients. VNS has probably a global modulatory effect on the immune system along with gut metabolic regulations. This pilot study needs replication in a larger randomized double-blinded control study.
Authors: Timir Datta-Chaudhuri; Theodoros Zanos; Eric H Chang; Peder S Olofsson; Stephan Bickel; Chad Bouton; Daniel Grande; Loren Rieth; Cynthia Aranow; Ona Bloom; Ashesh D Mehta; Gene Civillico; Molly M Stevens; Eric Głowacki; Christopher Bettinger; Martin Schüettler; Chris Puleo; Robert Rennaker; Saroj Mohanta; Daniela Carnevale; Silvia V Conde; Bruno Bonaz; David Chernoff; Suraj Kapa; Magnus Berggren; Kip Ludwig; Stavros Zanos; Larry Miller; Doug Weber; Daniel Yoshor; Lawrence Steinman; Sangeeta S Chavan; Valentin A Pavlov; Yousef Al-Abed; Kevin J Tracey Journal: Bioelectron Med Date: 2021-05-24
Authors: Anne S Ten Hove; David J Brinkman; Andrew Y F Li Yim; Caroline Verseijden; Theo B M Hakvoort; Iris Admiraal; Olaf Welting; Patricia H P van Hamersveld; Valérie Sinniger; Bruno Bonaz; Misha D Luyer; Wouter J de Jonge Journal: Bioelectron Med Date: 2020-10-28
Authors: Ivan Emmanuel Ramos-Martínez; María Carmen Rodríguez; Marco Cerbón; Juan Carlos Ramos-Martínez; Edgar Gustavo Ramos-Martínez Journal: Int J Mol Sci Date: 2021-12-14 Impact factor: 5.923