Cargando…

Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear

BACKGROUND: Rheumatoid arthritis (RA) is a chronic and debilitating inflammatory disease characterized by extensive joint tissue inflammation. Implantable bioelectronic devices targeting the inflammatory reflex reduce TNF production and inflammation in preclinical models of inflammatory disease, and...

Descripción completa

Detalles Bibliográficos
Autores principales: Addorisio, Meghan E., Imperato, Gavin H., de Vos, Alex F., Forti, Steve, Goldstein, Richard S., Pavlov, Valentin A., van der Poll, Tom, Yang, Huan, Diamond, Betty, Tracey, Kevin J., Chavan, Sangeeta S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098240/
https://www.ncbi.nlm.nih.gov/pubmed/32232095
http://dx.doi.org/10.1186/s42234-019-0020-4
_version_ 1783511154978455552
author Addorisio, Meghan E.
Imperato, Gavin H.
de Vos, Alex F.
Forti, Steve
Goldstein, Richard S.
Pavlov, Valentin A.
van der Poll, Tom
Yang, Huan
Diamond, Betty
Tracey, Kevin J.
Chavan, Sangeeta S.
author_facet Addorisio, Meghan E.
Imperato, Gavin H.
de Vos, Alex F.
Forti, Steve
Goldstein, Richard S.
Pavlov, Valentin A.
van der Poll, Tom
Yang, Huan
Diamond, Betty
Tracey, Kevin J.
Chavan, Sangeeta S.
author_sort Addorisio, Meghan E.
collection PubMed
description BACKGROUND: Rheumatoid arthritis (RA) is a chronic and debilitating inflammatory disease characterized by extensive joint tissue inflammation. Implantable bioelectronic devices targeting the inflammatory reflex reduce TNF production and inflammation in preclinical models of inflammatory disease, and in patients with RA and Crohn’s disease. Here, we assessed the effect of applying a vibrotactile device to the cymba concha of the external ear on inflammatory responses in healthy subjects, as well as its effect on disease activity in RA patients. METHODS: Six healthy subjects received vibrotactile treatment at the cymba concha, and TNF production was analyzed at different time points post-stimulation. In a separate study, nineteen healthy subjects were enrolled in a randomized cross-over study, and effects of vibrotactile treatment at either the cymba concha or gastrocnemius on cytokine levels were assessed. In addition, the clinical efficacy of vibrotactile treatment on disease activity in RA was assessed in nine patients with RA in a prospective interventional study. RESULTS: Vibrotactile treatment at the cymba concha reduced TNF levels, and the suppressive effect persisted up to 24 h. In the cross-over study with 19 healthy subjects, vibrotactile treatment at the cymba concha but not at the gastrocnemius significantly reduced TNF, IL-1β, and IL-6 levels compared to pre-treatment baseline (TNF p < 0.05, IL-6 p < 0.01, IL-1β p < 0.001). In healthy subjects, vibrotactile treatment at the cymba concha inhibited TNF by 80%, IL-6 by 73%, and IL-1β by 50% as compared to pre-treatment baseline levels. In RA patients, a significant decrease in DAS28-CRP scores was observed two days post-vibrotactile stimulation at the cymba concha (DAS28-CRP score pre-treatment = 4.19 ± 0.33 vs post-treatment = 3.12 ± 0.25, p < 0.05). Disease activity remained significantly reduced 7 days following vibrotactile treatment (DAS28-CRP score 7 days post-treatment = 2.79 ± 0.21, p < 0.01). In addition, a persistent improvement in visual analogue scale scores, a patient derived measure of global health assessment, was observed in RA patients following vibrotactile treatment. CONCLUSION: Application of a vibrotactile device to the cymba concha inhibits peripheral blood production of TNF, IL-1β, and IL-6 in healthy subjects, and attenuates systemic inflammatory responses in RA patients. TRIAL REGISTRATIONS: ClinicalTrials.gov Identifier: NCT01569789 and NCT00859859. The AMC trial conducted in The Netherlands does not have a ClinicalTrials.gov Identifier.
format Online
Article
Text
id pubmed-7098240
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-70982402020-03-30 Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear Addorisio, Meghan E. Imperato, Gavin H. de Vos, Alex F. Forti, Steve Goldstein, Richard S. Pavlov, Valentin A. van der Poll, Tom Yang, Huan Diamond, Betty Tracey, Kevin J. Chavan, Sangeeta S. Bioelectron Med Research Article BACKGROUND: Rheumatoid arthritis (RA) is a chronic and debilitating inflammatory disease characterized by extensive joint tissue inflammation. Implantable bioelectronic devices targeting the inflammatory reflex reduce TNF production and inflammation in preclinical models of inflammatory disease, and in patients with RA and Crohn’s disease. Here, we assessed the effect of applying a vibrotactile device to the cymba concha of the external ear on inflammatory responses in healthy subjects, as well as its effect on disease activity in RA patients. METHODS: Six healthy subjects received vibrotactile treatment at the cymba concha, and TNF production was analyzed at different time points post-stimulation. In a separate study, nineteen healthy subjects were enrolled in a randomized cross-over study, and effects of vibrotactile treatment at either the cymba concha or gastrocnemius on cytokine levels were assessed. In addition, the clinical efficacy of vibrotactile treatment on disease activity in RA was assessed in nine patients with RA in a prospective interventional study. RESULTS: Vibrotactile treatment at the cymba concha reduced TNF levels, and the suppressive effect persisted up to 24 h. In the cross-over study with 19 healthy subjects, vibrotactile treatment at the cymba concha but not at the gastrocnemius significantly reduced TNF, IL-1β, and IL-6 levels compared to pre-treatment baseline (TNF p < 0.05, IL-6 p < 0.01, IL-1β p < 0.001). In healthy subjects, vibrotactile treatment at the cymba concha inhibited TNF by 80%, IL-6 by 73%, and IL-1β by 50% as compared to pre-treatment baseline levels. In RA patients, a significant decrease in DAS28-CRP scores was observed two days post-vibrotactile stimulation at the cymba concha (DAS28-CRP score pre-treatment = 4.19 ± 0.33 vs post-treatment = 3.12 ± 0.25, p < 0.05). Disease activity remained significantly reduced 7 days following vibrotactile treatment (DAS28-CRP score 7 days post-treatment = 2.79 ± 0.21, p < 0.01). In addition, a persistent improvement in visual analogue scale scores, a patient derived measure of global health assessment, was observed in RA patients following vibrotactile treatment. CONCLUSION: Application of a vibrotactile device to the cymba concha inhibits peripheral blood production of TNF, IL-1β, and IL-6 in healthy subjects, and attenuates systemic inflammatory responses in RA patients. TRIAL REGISTRATIONS: ClinicalTrials.gov Identifier: NCT01569789 and NCT00859859. The AMC trial conducted in The Netherlands does not have a ClinicalTrials.gov Identifier. BioMed Central 2019-04-17 /pmc/articles/PMC7098240/ /pubmed/32232095 http://dx.doi.org/10.1186/s42234-019-0020-4 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Addorisio, Meghan E.
Imperato, Gavin H.
de Vos, Alex F.
Forti, Steve
Goldstein, Richard S.
Pavlov, Valentin A.
van der Poll, Tom
Yang, Huan
Diamond, Betty
Tracey, Kevin J.
Chavan, Sangeeta S.
Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear
title Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear
title_full Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear
title_fullStr Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear
title_full_unstemmed Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear
title_short Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear
title_sort investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098240/
https://www.ncbi.nlm.nih.gov/pubmed/32232095
http://dx.doi.org/10.1186/s42234-019-0020-4
work_keys_str_mv AT addorisiomeghane investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear
AT imperatogavinh investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear
AT devosalexf investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear
AT fortisteve investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear
AT goldsteinrichards investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear
AT pavlovvalentina investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear
AT vanderpolltom investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear
AT yanghuan investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear
AT diamondbetty investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear
AT traceykevinj investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear
AT chavansangeetas investigationaltreatmentofrheumatoidarthritiswithavibrotactiledeviceappliedtotheexternalear