Transcutaneous vagus nerve stimulation in erosive hand osteoarthritis: protocol for the randomised, double-blind, sham-controlled ESTIVAL trial

Abstract

Introduction Patients with erosive hand osteoarthritis (EHOA) experience pain and inflammation, two features that can be targeted by vagus nerve stimulation using electrical auricular transcutaneous vagus nerve stimulation (tVNS). A pilot study demonstrated the feasibility of the procedure, so we designed a randomised sham-controlled trial to determine the safety and efficacy of tVNS in EHOA. Methods and analysis ESTIVAL Study (Essai randomisé comparant la STImulation auriculaire transcutanée du nerf Vague versus sham stimulation dans l’Arthrose DigitaLe Érosive symptomatique et inflammatoire) is a superiority, randomised, double-blind sham-controlled trial comparing two parallel arms: active and sham tVNSs in a 1:1 ratio. Patients with symptomatic EHOA (score ≥40/100 mm on a visual analogue scale (VAS) for pain of 0–100 mm) and inflammatory EHOA (≥1 clinical and ultrasonography-determined interphalangeal synovitis) are included in 18 hospital centres (17 rheumatology and 1 rehabilitation departments) in France. Active and sham tVNSs use an auricular electrode connected to the Vagustim device, with no electric current delivered in the sham group. Patients undergo stimulation for 20 min/day for 12 weeks. The follow-up visits take place at weeks 4, 8 and 12. The enrolment duration is 2 years and started in April 2021; 156 patients are scheduled to be included. The primary outcome is the difference in self-reported hand pain in the previous 48 hours measured on a VAS of 0–100 mm between baseline and week 12. Secondary outcomes include other pain outcomes, function, quality of life, serum biomarker levels, compliance and tolerance. For a subset of patients, MRI of the hand is performed at baseline and week 12 to compare the change in Outcome Measures in Rheumatology/Hand Osteoarthritis MRI Scoring System subscores. The primary analysis will be performed at the end of the study according to the intent-to-treat principle. Ethics and dissemination Ethics approval was obtained from the institutional review board (Comité de Protection des Personnes, 2020-A02213-36). All participants will be required to provide written informed consent. The findings will be published in peer-reviewed journals. Trial registration number NCT04520516; Pre-results. Protocol version and number V.2 of 11 March 2021.

Role of the Sympathetic Nervous System in Mild Chronic Inflammatory Diseases: Focus on Osteoarthritis

“…Traditionally, vagus nerve stimulation (VNS) has been performed using an implanted electrical electrode which is connected to a subcutaneously implanted generator. Alternatively, the vagus nerve can also be stimulated percutaneously, providing a non-invasive technique [ 273 ]. Electrical stimulation of the vagus nerve is already approved as an anti-inflammatory therapy for refractory epilepsy and depression and is also being investigated for the treatment of musculoskeletal diseases, such as RA [ 9 , 274 ].…”

El Osteoartritinde Güncel Tedavi Yaklaşımları

“…Yakın zamanda, kulakta yer alan vagus siniri duyusal afferent dalını uyaran transkütanöz VSS, noninvaziv bir VSS metodu olarak bazı ağrılı ve inflamatuvar durumlarda çalışılmaya başlanmıştır. Çok merkezli sham kontrollü randomize çift-kör bir çalışmada (ESTIVAL çalışması) eroziv el OA'lı hastalarda auriküler transkütanöz VSS'un etkinliği ve güvenliliği araştırılmakta olup yakın zamanda sonuçlarının yayınlanması beklenen bu innovatif çalışmada ilgili modalitenin sham uygulamaya karşı elde ağrıyı azaltıp, fonksiyonu iyileştirilmesi hipotezi sınanmaktadır 44 .…”