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

Condition(s) studied

Investigational drug(s) / intervention(s)

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.

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.

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.

Eligibility

Primary outcome measure(s)

• ACR 20 response — 12 weeks
  Difference between treatment and control groups in the proportion of subjects who achieve ACR 20; defined as at least 20% improvement from baseline to day 84 (12w) in tender and swollen joint counts of 28 joints (scale 0=best to 28=worse) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (0-3), subject global assessment VAS, subject pain VAS, evaluator's global assessment VAS (0=best to 10=worse), or high sensitivity C-reactive protein (hsCRP) concentration (mg/mL) with higher values representing worse outcome.

Trial sites (6)

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