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

NCT06779123 | Recruiting

• 1 other identifier: 5.1-2024-6593
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 6

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.

Conditions

Rheumatoid Arthritis (RA)

Keywords

Arthritis; Pain; DMARD

Outcome Measures

Primary Outcomes (1)

• ACR 20 response

  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.

  12 weeks

Secondary Outcomes (1)

• ACR 50 response

  12 weeks

Study Arms (2)

Arm A: Transauricular stimulation

EXPERIMENTAL

Stimulation in the ear will be performed for 5 min twice daily for 12 weeks.

Device: Transauricular vagus nerve stimulation.

Arm B: Transauricular non-stimulation

SHAM COMPARATOR

The device is placed to the ear but no stimulation will occur. The procedure is performed for 5 min twice daily for 12 weeks.

Device: transauricular vagus nerve non-stimulation

Interventions

Transauricular vagus nerve stimulation. DEVICE

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.

Arm A: Transauricular stimulation

transauricular vagus nerve non-stimulation DEVICE

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.

Arm B: Transauricular non-stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• taVNS AB: lead
• Karolinska Institutet: collaborator

Study Sites (6)

Section for Rheumatology, Skåne University Hospital, Lund

Lund, Skåne County, SE 22185, Sweden

RECRUITING

Section for Rheumatology, Skåne University Hospital, Malmö

Malmo, 20502, Sweden

RECRUITING

Dept of Rheumatology, Örebro University Hospital

Örebro, 70116, Sweden

RECRUITING

Center for Rheumatology, Academic Specialist Centre

Stockholm, 17176, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, 17176, Sweden

RECRUITING

Dept of Rheumatology, Umeå University Hospital

Umeå, 90189, Sweden

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis; Pain

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Ulf Andersson, Professor

  taVNS AB

  STUDY DIRECTOR

Central Study Contacts

Jon Lampa, Professor

CONTACT

+46 12370000; jon.lampa@ki.se

Linda Regner-Dyberg, Secretary

CONTACT

+46812370000; linda.regner-dyberg@regionstockholm.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Auricular stimulation

Study Record Dates

• First Submitted: January 7, 2025
• First Posted: January 16, 2025
• Study Start: March 21, 2025
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): June 15, 2027
• Last Updated: September 10, 2025

Record last verified: 2025-01

Locations

SE (6)