Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study Protocol
Axial spondyloarthritis (SpA), is a major cause of chronic pain and disability that profoundly alters the quality of life of patients. Nearly half of patients with SpA usually develop drug resistance. Non-pharmacological treatments targeting inflammation are an attractive alternative to drug adminis...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Human Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnhum.2021.679775/full |
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| author | Eric Azabou Eric Azabou Guillaume Bao Guillaume Bao Félicie Costantino Félicie Costantino Félicie Costantino Madalina Jacota Chanez Lazizi Lionelle Nkam Martin Rottman Martin Rottman Anne-Laure Roux Anne-Laure Roux Sylvain Chevallier Lamiae Grimaldi Maxime Breban Maxime Breban Maxime Breban |
| author_facet | Eric Azabou Eric Azabou Guillaume Bao Guillaume Bao Félicie Costantino Félicie Costantino Félicie Costantino Madalina Jacota Chanez Lazizi Lionelle Nkam Martin Rottman Martin Rottman Anne-Laure Roux Anne-Laure Roux Sylvain Chevallier Lamiae Grimaldi Maxime Breban Maxime Breban Maxime Breban |
| author_sort | Eric Azabou |
| collection | DOAJ |
| description | Axial spondyloarthritis (SpA), is a major cause of chronic pain and disability that profoundly alters the quality of life of patients. Nearly half of patients with SpA usually develop drug resistance. Non-pharmacological treatments targeting inflammation are an attractive alternative to drug administration. Vagus nerve stimulation (VNS), by promoting a cholinergic anti-inflammatory reflex holds promise for treating inflammatory disease. Inflammatory reflex signaling, which is enhanced by electrically stimulating the vagus nerve, significantly reduces cytokine production and attenuates disease severity in animal models of endotoxemia, sepsis, colitis, and other preclinical models of inflammatory diseases. It has been proposed that vagal efferent fibers release acetylcholine (Ach), which can interact with α7-subunit-containing nicotinic receptors expressed by tissue macrophages and other immune cells to rapidly inhibit the synthesis/release of pro-inflammatory cytokines such as TNFα, IL-1β, IL-6, and IL-18. External vagal nerve stimulation devices are now available that do not require surgery nor implantation to non-invasively stimulate the vagal nerve. This double-blind randomized cross-over clinical trial aims to study the change in SpA disease activity, according to Assessment in Ankylosing Spondylitis 20 (ASAS20) definition, after 12 weeks of non-invasive VNS treatment vs. non-specific dummy stimulation (control group). One hundred and twenty adult patients with drug resistant SpA, meeting the ASAS classification criteria, will be included in the study. Patients will be randomized into two parallel groups according to a cross over design: either active VNS for 12 weeks, then dummy stimulation for 12 weeks, or dummy stimulation for 12 weeks, then active VNS for 12 weeks. The two stimulation periods will be separated by a 4 weeks wash-out period. A transcutaneous auricular vagus nerve stimulator Tens Eco Plus SCHWA MEDICOTM France will be used in this study. The active VNS stimulation will be applied in the cymba conchae of the left ear upon the auricular branch of the vagus nerve, using low intensity (2–5 mA), once à week, during 1 h. Dummy stimulation will be performed under the same conditions and parameters as active VNS stimulation, but at an irrelevant anatomical site: the left ear lobule. This multicenter study was registered on ClinicalTrials.gov: NCT04286373. |
| first_indexed | 2024-12-14T17:56:45Z |
| format | Article |
| id | doaj.art-fecf8f994ff5441ebf840add30a3090f |
| institution | Directory Open Access Journal |
| issn | 1662-5161 |
| language | English |
| last_indexed | 2024-12-14T17:56:45Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Human Neuroscience |
| spelling | doaj.art-fecf8f994ff5441ebf840add30a3090f2022-12-21T22:52:32ZengFrontiers Media S.A.Frontiers in Human Neuroscience1662-51612021-06-011510.3389/fnhum.2021.679775679775Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study ProtocolEric Azabou0Eric Azabou1Guillaume Bao2Guillaume Bao3Félicie Costantino4Félicie Costantino5Félicie Costantino6Madalina Jacota7Chanez Lazizi8Lionelle Nkam9Martin Rottman10Martin Rottman11Anne-Laure Roux12Anne-Laure Roux13Sylvain Chevallier14Lamiae Grimaldi15Maxime Breban16Maxime Breban17Maxime Breban18Clinical Neurophysiology and Neuromodulation Unit, Department of Physiology, Raymond Poincaré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, FranceLaboratory of Infection and Inflammation (2I)–Inserm UMR 1173, University of Versailles Saint-Quentin en Yvelines (UVSQ), Paris-Saclay University, Paris, FranceClinical Neurophysiology and Neuromodulation Unit, Department of Physiology, Raymond Poincaré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, FranceLaboratory of Infection and Inflammation (2I)–Inserm UMR 1173, University of Versailles Saint-Quentin en Yvelines (UVSQ), Paris-Saclay University, Paris, FranceLaboratory of Infection and Inflammation (2I)–Inserm UMR 1173, University of Versailles Saint-Quentin en Yvelines (UVSQ), Paris-Saclay University, Paris, FranceRheumatology Department, AP-HP, Ambroise Paré Hospital, AP-HP, Boulogne-Billancourt, FranceLaboratory of Excellence Inflamex, Paris Descartes University, Sorbonne Paris Cité, Paris, FranceClinical Research Unit, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Boulogne-Billancourt, France, University of Versailles Saint-Quentin en Yvelines, Paris-Saclay University, Paris, FranceClinical Research Unit, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Boulogne-Billancourt, France, University of Versailles Saint-Quentin en Yvelines, Paris-Saclay University, Paris, FranceClinical Research Unit, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Boulogne-Billancourt, France, University of Versailles Saint-Quentin en Yvelines, Paris-Saclay University, Paris, FranceLaboratory of Infection and Inflammation (2I)–Inserm UMR 1173, University of Versailles Saint-Quentin en Yvelines (UVSQ), Paris-Saclay University, Paris, FranceMicrobiology Laboratory, Raymond Poincaré Hospital, AP-HP Paris Saclay University, Paris, FranceLaboratory of Infection and Inflammation (2I)–Inserm UMR 1173, University of Versailles Saint-Quentin en Yvelines (UVSQ), Paris-Saclay University, Paris, FranceMicrobiology Laboratory, Raymond Poincaré Hospital, AP-HP Paris Saclay University, Paris, FranceVersailles Engineering Systems Laboratory (LISV), University of Versailles Saint Quentin en Yvelines (UVSQ), Vélizy, FranceClinical Research Unit, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Boulogne-Billancourt, France, University of Versailles Saint-Quentin en Yvelines, Paris-Saclay University, Paris, FranceLaboratory of Infection and Inflammation (2I)–Inserm UMR 1173, University of Versailles Saint-Quentin en Yvelines (UVSQ), Paris-Saclay University, Paris, FranceRheumatology Department, AP-HP, Ambroise Paré Hospital, AP-HP, Boulogne-Billancourt, FranceLaboratory of Excellence Inflamex, Paris Descartes University, Sorbonne Paris Cité, Paris, FranceAxial spondyloarthritis (SpA), is a major cause of chronic pain and disability that profoundly alters the quality of life of patients. Nearly half of patients with SpA usually develop drug resistance. Non-pharmacological treatments targeting inflammation are an attractive alternative to drug administration. Vagus nerve stimulation (VNS), by promoting a cholinergic anti-inflammatory reflex holds promise for treating inflammatory disease. Inflammatory reflex signaling, which is enhanced by electrically stimulating the vagus nerve, significantly reduces cytokine production and attenuates disease severity in animal models of endotoxemia, sepsis, colitis, and other preclinical models of inflammatory diseases. It has been proposed that vagal efferent fibers release acetylcholine (Ach), which can interact with α7-subunit-containing nicotinic receptors expressed by tissue macrophages and other immune cells to rapidly inhibit the synthesis/release of pro-inflammatory cytokines such as TNFα, IL-1β, IL-6, and IL-18. External vagal nerve stimulation devices are now available that do not require surgery nor implantation to non-invasively stimulate the vagal nerve. This double-blind randomized cross-over clinical trial aims to study the change in SpA disease activity, according to Assessment in Ankylosing Spondylitis 20 (ASAS20) definition, after 12 weeks of non-invasive VNS treatment vs. non-specific dummy stimulation (control group). One hundred and twenty adult patients with drug resistant SpA, meeting the ASAS classification criteria, will be included in the study. Patients will be randomized into two parallel groups according to a cross over design: either active VNS for 12 weeks, then dummy stimulation for 12 weeks, or dummy stimulation for 12 weeks, then active VNS for 12 weeks. The two stimulation periods will be separated by a 4 weeks wash-out period. A transcutaneous auricular vagus nerve stimulator Tens Eco Plus SCHWA MEDICOTM France will be used in this study. The active VNS stimulation will be applied in the cymba conchae of the left ear upon the auricular branch of the vagus nerve, using low intensity (2–5 mA), once à week, during 1 h. Dummy stimulation will be performed under the same conditions and parameters as active VNS stimulation, but at an irrelevant anatomical site: the left ear lobule. This multicenter study was registered on ClinicalTrials.gov: NCT04286373.https://www.frontiersin.org/articles/10.3389/fnhum.2021.679775/fullaxial spondyloarthritismedical devicevagus nervetrialprotocolneuromodulation |
| spellingShingle | Eric Azabou Eric Azabou Guillaume Bao Guillaume Bao Félicie Costantino Félicie Costantino Félicie Costantino Madalina Jacota Chanez Lazizi Lionelle Nkam Martin Rottman Martin Rottman Anne-Laure Roux Anne-Laure Roux Sylvain Chevallier Lamiae Grimaldi Maxime Breban Maxime Breban Maxime Breban Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study Protocol Frontiers in Human Neuroscience axial spondyloarthritis medical device vagus nerve trial protocol neuromodulation |
| title | Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study Protocol |
| title_full | Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study Protocol |
| title_fullStr | Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study Protocol |
| title_full_unstemmed | Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study Protocol |
| title_short | Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study Protocol |
| title_sort | randomized cross over study assessing the efficacy of non invasive stimulation of the vagus nerve in patients with axial spondyloarthritis resistant to biotherapies the esnv spa study protocol |
| topic | axial spondyloarthritis medical device vagus nerve trial protocol neuromodulation |
| url | https://www.frontiersin.org/articles/10.3389/fnhum.2021.679775/full |
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