Treatment With Auricular Vagus Nerve Stimulation in Rheumatoid Arthritis - the TRAVAGA Study

Summary

Purpose and aim

The overall aim is to investigate efficacy and safety of a newly developed non-invasive auricular investigational device that electrically stimulates the auricular branch of the vagus nerve to activate the cholinergic anti-inflammatory mechanism to treat rheumatoid arthritis patients not responding to standard therapy. The mode of treatment is termed transcutaneous auricular vagus nerve stimulation (taVNS). Specifically, the investigators will address the following research questions:

The investigation is a multicenter, placebo-controlled, randomized, double-blinded, superiority, clinical study to evaluate the safety and efficacy of a novel transcutaneous auricular vagus nerve stimulator system, termed TRAVAGUS, in patients with moderate-to-severe rheu-matoid arthritis (RA) who are incomplete responders or are intolerant to biologic or targeted synthetic disease modifying anti-rheumatic drugs (DMARDs). The primary efficacy endpoint is the proportion of patients achieving an ACR20 response (a composite measure of the effectiveness of arthritis treatments set forth by the American College of Rheumatology) in the treatment group compared to sham group at 12 weeks. Electrical vagus nerve stimulation is an investigational anti-inflammatory therapy targeting the nervous system to modulate immune activity. RA is a global disease associated with significant reduced quality of life and very high health care costs substantially driven by therapeutics. While many with RA have benefited from modern era biologic and small molecule therapies, unresolved chronic inflammation is common despite treatment. Therefore, non-toxic, lower cost anti-inflammatory, non-pharmacologic therapy is needed.

Note: This study relates to a FDA-nonregulated Drug and FDA-nonregulated Device. There are no U.S. Locations for the study. The study was approved by EMA.

Conditions

• Rheumatoid Arthritis (RA)

Interventions

DEVICE

Transauricular vagus nerve stimulation.

TRAVAGUS is a portable electrical vagus nerve stimulator device that non-invasively activates the auricular branch of the vagus nerve in the left ear. The system consists of two units, the electrical stimulator and the ear electrodes that are mounted in a headset. The electrical signals are delivered transcutaneously to the ear via two separate cables connected to two aluminium electrodes. There is no need for electrode gel application on the auricular skin, since the conductivity of the two metallic electrodes is fully sufficient for functional electrical contact. The device is powered by 4 x 1,5V AAA batteries. The electrical source is a CE-marked tens unit termed STIM-PRO X9+, AXION GmbH, Leonberg, Germany. The investigational headset with auricular electrodes is designed and manufactured by taVNS AB in Saltsjö-Duvnäs, Sweden. Stimulation will be performed for 5 min twice daily for 12 weeks.

DEVICE

transauricular vagus nerve non-stimulation

TRAVAGUS is a portable electrical vagus nerve stimulator device that non-invasively activates the auricular branch of the vagus nerve in the left ear. The system consists of two units, the electrical stimulator and the ear electrodes that are mounted in a headset. The device is placed to the ear but no stimulation will occur. The procedure is performed for 5 min twice daily for 12 weeks.

Sponsors & Collaborators

• Karolinska Institutet

  collaborator OTHER

• taVNS AB

  lead INDUSTRY

Principal Investigators

• Ulf Andersson, Professor · taVNS AB

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-03-21

Primary Completion

2026-10-15

Completion

2027-06-15

Countries

• Sweden

Study Locations