Transcutaneous Cervical Vagus Nerve Stimulation (tcVNS) in JIA

NCT05710640 | Terminated Phase 2 Results DMC FDA Device

• 1 other identifier: DAIT AJA01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

Brief Summary

The study is a multicenter, double-blind, sham-controlled trial to evaluate the safety and effectiveness of tcVNS on pain and inflammation associated with JIA. tcVNS is administered with a device that gives off mild electrical impulses through the skin to stimulate the vagus nerve. Part of the vagus nerve and its branches are located in the head and neck. For this study, the impulses will be administered using a small electrode at the cymba concha for participants receiving treatment with active tcVNS and at the neck for participants receiving sham stimulation. The electrode helps to conduct the stimulation through the skin. This stimulation triggers a chemical response through the nerves and has been found to be effective in reducing pain and inflammation in several diseases. The primary objective of this study is to determine the effect of tcVNS on JIA ACR 50 in participants with active JIA. The components of the active and sham tcVNS devices, utilizing the Roscoe Medical TENS 7000, have been FDA 510(k)-cleared and have been determined by the IRB to be a nonsignificant risk device.

Conditions

Juvenile Idiopathic Arthritis (JIA)

Keywords

Juvenile Idiopathic Arthritis; JIA; Children; tcVNS; Cytokines; Inflammation; Nonsignificant risk; NSR

Outcome Measures

Primary Outcomes (1)

• Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Responders at Week 8 Compared to Baseline

  The JIA ACR 50 is a validated composite response consisting of 6 core criteria: number of joints with active arthritis; number of joints with limited motion; physician's assessment of disease activity (measured on a 10 cm visual analogue scale (VAS)); parent/patient assessment of overall well-being (measured on a 10 cm VAS); a validated measure of physical function, Childhood Health Assessment Questionnaire (CHAQ); and a laboratory measure of inflammation, c-Reactive Protein (CRP). The JIA ACR 50 is achieved if 3 of any 6 core set variables improved by at least 50% from Baseline, and no more than 1 variable worsens by \>30%. A negative change from Baseline in any of the core set variables signifies improvement. Participants missing any of the JIA ACR core criteria at Week 8 are imputed as JIA ACR 50 non-responders at Week 8.

  Week 8

Secondary Outcomes (13)

• Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Responders at Weeks 4, 12, and 16 Compared to Baseline

  Weeks 4, 12, 16

• Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Responders at Weeks 4, 8, 12, and 16 Compared to Baseline

  Weeks 4, 8, 12, 16

• Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Responders at Week 4, 8, 12, and 16 Compared to Baseline

  Weeks 4, 8, 12, 16

• Change From Baseline in Juvenile Arthritis Disease Activity Score in 27 Joints (JADAS-27) at Weeks 4, 8, 12, and 16

  Baseline; Weeks 4, 8, 12, 16

• Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Responders at Weeks 12 and 16 Compared to Week 8

  Week 12 and 16

Study Arms (2)

Blinded phase

EXPERIMENTAL

Participants will receive 5 minutes of active tcVNS or sham tcVNS daily for 8 weeks.

Device: Active tcVNS; Device: Sham tcVNS

Open-Label phase

EXPERIMENTAL

Participants will receive 5 minutes of stimulation via the active tcVNS device for 8 weeks after a double-blind, sham-controlled 8- week period.

Device: Active tcVNS

Interventions

Active tcVNS DEVICE

Participants being treated with an active tcVNS device will attach the stimulator, lead, and clip electrode to assemble the complete device and coat the electrode surfaces with electrode gel. The electrode will be placed on the cymba concha of a left ear that is free of earrings or other objects, cleaned internally and externally, and coated with a thin layer of electrode gel. The participant will gradually advance the stimulator knob clockwise until they feel the electrical stimulation at a level that is easily tolerated for 5 minutes and is not painful. The participant will apply the stimulation for 5 minutes, then the participant will turn off the stimulator, remove the electrode from the ear, and clean the ear and electrodes with gauze.

Also known as: tVNS, Active tVNS, taVNS, Active taVNS

Blinded phase

Sham tcVNS DEVICE

Participants being treated with a sham tcVNS device will place adhesive electrodes on the left side of the neck, which has had neck jewelry removed and has been cleaned at the site of treatment. The participant will then connect the lead to the electrodes and the stimulator to assemble the complete sham tcVNS device. The participant will gradually advance the stimulator knob clockwise until they feel the electrical stimulation at a level that is easily tolerated for 5 minutes and is not painful. Participants in this group will be instructed to not turn the knob above "3" on the dial as this is the maximum acceptable treatment level at the neck. The participant will apply the stimulation for 5 minutes, then the participant will turn off the stimulator, remove the electrode from the neck, and dispose of the electrodes.

Also known as: tVNS, Sham tVNS, taVNS, Sham taVNS, Sham Stimulation

Blinded phase

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant is 5 through 18 years of age (inclusive) at screening.
• Regarding informed consent and compliance:
• If 5 through 6 years of age, the participant's guardian is willing and able to understand and provide informed consent and comply with study protocol.
• If 7 through 17 years of age, the participant is willing and able to sign assent and comply with study protocol, and the participant's guardian is willing and able to understand and provide informed consent and comply with study protocol.
• If 18 years of age, the participant is willing and able to understand and provide informed consent and comply with study protocol.
• The participant has a Juvenile Idiopathic Arthritis (JIA) diagnosis meeting International League of Associations for Rheumatology (ILAR) classification criteria with one of the following subtypes:
• rheumatoid-factor negative polyarthritis
• rheumatoid-factor positive polyarthritis
• persistent oligoarthritis
• extended oligoarthritis
• psoriatic arthritis
• enthesitis-related arthritis
• systemic arthritis
• The participant has \>=3 joints with active arthritis at screening
• If the participant is receiving therapy for JIA at screening, that therapy is stable for the time period outlined below and is expected to remain stable for the duration of the study:

You may not qualify if:

• Other than NSAIDs or intra-articular injections, participant has been treated for JIA with lack of efficacy with:
• More than 2 different classes of therapies, or
• More than 3 medications in total
• Participant has received high-dose steroids (\>=0.2 mg/kg/day) within the 28 days prior to screening.
• Participant has had active systemic disease (fever, systemic rash) within the 3 months prior to screening including any of the following lab manifestations at screening:
• Ferritin \>1000 ng/mL
• White blood cell (WBC) ≥15,000/mm\^3
• Participant has had an active acute systemic infection within 2 weeks of screening. involving fever (100.4⁰F or higher) for more than 24 hours, requirement for systemic antibiotics or antivirals, GI symptoms lasting 48 hours or more, or the need to hold second line medications for JIA (methotrexate or biologic).
• Participant has a history of arrhythmia.
• Participant has been diagnosed with postural orthostatic tachycardia syndrome (POTS).
• Participant has received an intra-articular cortisone injection within the 28 days prior to screening.
• Participant has received treatment with an investigational drug or device during the 28 days prior to screening or within five half-lives of the investigational drug prior to screening/baseline, whichever is the greater length of time.
• Participant has received chronic treatment with an anti-cholinergic medication, including over the counter medications.
• Participant has received treatment with rituximab:
• Within one year of screening

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence (ACE): collaborator
• Northwell Health: collaborator

Study Sites (7)

University of California San Francisco School of Medicine: Department of Pediatrics, Division of Pediatric Rheumatology

San Francisco, California, 94158, United States

Location

Nemours Children's Health: Department of Pediatric Rheumatology

Orlando, Florida, 32827, United States

Location

Indiana University Medical Center: Riley Hospital for Children Department of Pediatric Rheumatology

Indianapolis, Indiana, 46202, United States

Location

Feinstein Institutes for Medical Research, Cohen Children's Medical Center: Pediatric Rheumatology

Lake Success, New York, 11040, United States

Location

Stephen D. Hassenfield Children's Center at NYU Langone Health

New York, New York, 10016, United States

Location

Division of Pediatric Rheumatology at the University of Utah School of Medicine and Primary Children's Hospital

Salt Lake City, Utah, 84132, United States

Location

Seattle Children's Hospital: Rheumatology Clinic

Seattle, Washington, 98105, United States

Location

Related Links

• Autoimmunity Centers of Excellence (ACE)
• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Conditions

Arthritis, Juvenile; Inflammation

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Beth Gottlieb, MD

  Feinstein Institutes for Medical Research, Cohen Children's Medical Center: Pediatric Rheumatology

  STUDY CHAIR

• Cynthia Aranow, MD

  Northwell Health

  STUDY CHAIR

• Timir Datta-Chaudhuri, PhD

  Northwell Health

  STUDY CHAIR

• Betty Diamond, MD

  Northwell Health

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2023
• First Posted: February 2, 2023
• Study Start: June 27, 2023
• Primary Completion: November 13, 2024
• Study Completion: January 15, 2025
• Last Updated: November 25, 2025
• Results First Posted: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

US (7)