Treatment With Auricular Vagus Nerve Stimulation in Rheumatoid Arthritis - the TRAVAGA Study
Trial Parameters
Brief 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 Criteria
Inclusion Criteria: * \> 18 years of age on day of signing informed consent * Active RA, DAS28\>3.2, at least 4/28 tender and 4/28 swollen joints * Demonstrated an inadequate response, loss of response, or intolerance to one or more approved for rheumatoid arthritis biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), including Janus kinase inhibitors. * Stable dose of glucocorticoids or conventional disease-modifying agents in RA (csDMARDs) at least 2 and 4 weeks, respectively, before screening Exclusion Criteria: * History of vagotomy * Partial or complete splenectomy * Recurrent vasovagal syncope episodes * Untreated or poorly controlled psychiatric illness * Significant immunodeficiency due to underlying illness * History of cerebrovascular insult * Clinically significant cardiovascular disease * Uncontrolled fibromyalgia * Pregnancy (if sexually active, using reliable form of birth control or being at least 2 yrs post-menopausal)