Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear | Bioelectronic Medicine | Full Text

Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear | Bioelectronic Medicine | Full Text

Bioelectronic Medicine

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

• Meghan E. Addorisio†,
• Gavin H. Imperato†,
• Alex F. de Vos,
• Steve Forti,
• Richard S. Goldstein,
• Valentin A. Pavlov,
• Tom van der Poll,
• Huan Yang,
• Betty Diamond,
• Kevin J. Tracey†Email author and
• Sangeeta S. Chavan†Email author

†Contributed equally

Bioelectronic Medicine20195:4

https://doi.org/10.1186/s42234-019-0020-4

©  The Author(s) 2019

• Received: 31 January 2019
• Accepted: 8 March 2019
• Published: 17 April 2019

Abstract

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.govIdentifier.

Keywords

• Auricular vagus nerve
• taVNS
• rheumatoid arthritis
• TNF