NCT05710640: AJA01

Transcutaneous Cervical Vagus Nerve Stimulation (tcVNS) in JIA

Terminated Phase 2 Results posted Last updated 25 November 2025

What this trial tests

Phase 2 trial testing Active tcVNS in Juvenile Idiopathic Arthritis (JIA) in 18 participants. Terminated before completion.

Timeline

27 June 2023

Primary endpoint
13 November 2024

15 January 2025

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	18
Start date	27 June 2023
Primary completion	13 November 2024
Estimated completion	15 January 2025
Sites	7 locations across United States

Drugs / interventions tested

• Active tcVNS
• Sham tcVNS
• Active tcVNS

Conditions studied

• Juvenile Idiopathic Arthritis (JIA) — all drugs for Juvenile Idiopathic Arthritis (JIA) →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 5 to 18, any sex, with Juvenile Idiopathic Arthritis (JIA). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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 t

Group	Value	95% CI
Active tcVNS	0.250	0.032 – 0.651
Sham Stimulation	0.333	0.075 – 0.701

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

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 t

Week 4

Group	Value	95% CI
Active tcVNS	0.375	0.085 – 0.755
Sham Stimulation	0.111	0.003 – 0.482

Week 12

Group	Value	95% CI
Active tcVNS	0.625	0.245 – 0.915
Sham Stimulation	0.444	0.137 – 0.788

Week 16

Group	Value	95% CI
Active tcVNS	0.625	0.245 – 0.915
Sham Stimulation	0.556	0.212 – 0.863

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

The JIA ACR 30 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 30 is achieved if 3 of any 6 core set variables improved by at least 30% from Baseline, and no more t

Week 4

Group	Value	95% CI
Active tcVNS	0.500	0.157 – 0.843
Sham Stimulation	0.556	0.212 – 0.863

Week 8

Group	Value	95% CI
Active tcVNS	0.375	0.085 – 0.755
Sham Stimulation	0.444	0.137 – 0.788

Week 12

Group	Value	95% CI
Active tcVNS	0.750	0.349 – 0.968
Sham Stimulation	0.556	0.212 – 0.863

Week 16

Group	Value	95% CI
Active tcVNS	0.875	0.473 – 0.997
Sham Stimulation	0.667	0.299 – 0.925

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

The JIA ACR 70 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 70 is achieved if 3 of any 6 core set variables improved by at least 70% from Baseline, and no more t

Week 4

Group	Value	95% CI
Active tcVNS	0.125	0.003 – 0.527
Sham Stimulation	0.111	0.003 – 0.482

Week 8

Group	Value	95% CI
Active tcVNS	0.125	0.003 – 0.527
Sham Stimulation	0.111	0.003 – 0.482

Week 12

Group	Value	95% CI
Active tcVNS	0.250	0.032 – 0.651
Sham Stimulation	0.333	0.075 – 0.701

Week 16

Group	Value	95% CI
Active tcVNS	0.500	0.157 – 0.843
Sham Stimulation	0.333	0.075 – 0.701

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

The JADAS-27 is a measurement of disease activity and is determined by adding the scores of its 4 components: 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); number of joints with active arthritis; and a laboratory measure of inflammation, c-Reactive Protein (CRP), normalized to a value between 0 and 10. The JADAS-27 includes the following joints: cervical spine, elbows, wrists, metacarpophalangeal joints (from first to third), proximal inter-phalangeal joints, hips, knees,

Week 4

Group	Value	95% CI
Active tcVNS	-5.187	-9.741 – -0.633
Sham Stimulation	-2.350	-6.366 – 1.666

Week 8

Group	Value	95% CI
Active tcVNS	-5.463	-9.624 – -1.303
Sham Stimulation	-3.657	-7.312 – -0.003

Week 12

Group	Value	95% CI
Active tcVNS	-9.647	-12.525 – -6.768
Sham Stimulation	-7.607	-10.297 – -4.917

Week 16

Group	Value	95% CI
Active tcVNS	-9.722	-13.267 – -6.178
Sham Stimulation	-6.256	-9.568 – -2.943

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

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 Week 8, and no more tha

Week 12

Group	Value	95% CI
Active tcVNS	0.125	0.003 – 0.527
Sham Stimulation	0.444	0.137 – 0.788

Week 16

Group	Value	95% CI
Active tcVNS	0.250	0.032 – 0.651
Sham Stimulation	0.333	0.075 – 0.701

Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Responders at Weeks 12 and 16 Compared to Week 8 Secondary · At Weeks 12 and 16

The JIA ACR 30 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 30 is achieved if 3 of any 6 core set variables improved by at least 30% from Week 8, and no more tha

Week 12

Group	Value	95% CI
Active tcVNS	0.250	0.032 – 0.651
Sham Stimulation	0.556	0.212 – 0.863

Week 16

Group	Value	95% CI
Active tcVNS	0.375	0.085 – 0.755
Sham Stimulation	0.333	0.075 – 0.701

Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Responders at Week 12 and 16 Compared to Week 8 Secondary · Weeks 12 and 16

The JIA ACR 70 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 70 is achieved if 3 of any 6 core set variables improved by at least 70% from Week 8, and no more tha

Week 12

Group	Value	95% CI
Active tcVNS	0.000	0.000 – 0.369
Sham Stimulation	0.111	0.003 – 0.482

Week 16

Group	Value	95% CI
Active tcVNS	0.000	0.000 – 0.369
Sham Stimulation	0.222	0.028 – 0.600

Change From Week 8 in Juvenile Arthritis Disease Activity Score in 27 Joints (JADAS-27) Secondary · Weeks 12 and 16

The JADAS-27 is a measurement of disease activity and is determined by adding the scores of its 4 components: 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); number of joints with active arthritis; and a laboratory measure of inflammation, c-Reactive Protein (CRP) normalized to a value between 0-10. The JADAS-27 includes the following joints: cervical spine, elbows, wrists, metacarpophalangeal joints (from first to third), proximal inter-phalangeal joints, hips, knees, and a

Week 12

Group	Value	95% CI
Active tcVNS	-5.216	-7.705 – -2.728
Sham Stimulation	-4.334	-6.653 – -2.015

Week 16

Group	Value	95% CI
Active tcVNS	-5.211	-8.559 – -1.863
Sham Stimulation	-3.053	-6.173 – 0.068

Longitudinal Trends From Baseline to Week 16 in Juvenile Arthritis Disease Activity Score in 27 Joints (JADAS-27) Secondary · Baseline; Weeks 4, 8, 12, 16

The JADAS-27 is a measurement of disease activity and is determined by adding the scores of its 4 components: 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); number of joints with active arthritis; and a laboratory measure of inflammation, c-Reactive Protein (CRP) normalized to a value between 0-10. The JADAS-27 includes the following joints: cervical spine, elbows, wrists, metacarpophalangeal joints (from first to third), proximal inter-phalangeal joints, hips, knees, and a

Baseline

Group	Value	95% CI
Active tcVNS	16.200	± 2.5385
Sham Stimulation	15.729	± 1.6774

Week 4

Group	Value	95% CI
Active tcVNS	10.957	± 2.7589
Sham Stimulation	13.445	± 2.2339

Week 8

Group	Value	95% CI
Active tcVNS	8.686	± 1.8442
Sham Stimulation	11.767	± 1.9662

Week 12

Group	Value	95% CI
Active tcVNS	4.331	± 0.8174
Sham Stimulation	7.150	± 1.8689

Week 16

Group	Value	95% CI
Active tcVNS	4.100	± 1.0433
Sham Stimulation	8.638	± 2.4012

Number of Participants With a Treatment-emergent Adverse Event From Day 0 to Week 8. Secondary · Day 0 to Week 8

A participant who experienced any of the following untoward or unfavorable medical occurrence(s) associated with the investigational device or any study mandated procedures following the first stimulation on Day 0 and prior to the Week 8 visit: * Grade 1 or higher mild palpitations, documented arrhythmia, or any unpleasant sensations caused by palpitations * Grade 1 or higher stimulation site reactions such as cutaneous irritation, pain, or skin burns * Grade 1 or higher Ear and labyrinth disorders as listed in the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except those of t

Group	Value	95% CI
Blinded Phase: Active tcVNS	3
Blinded Phase: Sham Stimulation	0

Number of Participants With a Treatment-emergent Adverse Event From Week 8 to Week 16 Secondary · Week 8 to Week 16

A participant who experienced any of the following untoward or unfavorable medical occurrence(s) associated with the investigational device or any study mandated procedures between Week 8 and Week 16: * Grade 1 or higher mild palpitations, documented arrhythmia, or any unpleasant sensations caused by palpitations * Grade 1 or higher stimulation site reactions such as cutaneous irritation, pain, or skin burns * Grade 1 or higher Ear and labyrinth disorders as listed in the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except those of the middle ear * Grade 1 or higher JIA flares

Group	Value	95% CI
Open-Label Phase: Active tcVNS Following Active tcVNS	2
Open-Label Phase: Active tcVNS Following Sham Stimulation	1

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events were recorded in EDC from after initiation of stimulation at Day 0 to Week 16.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Blinded Phase: Active tcVNS

Serious: 0/8 (0%)

Deaths: 0/8

Blinded Phase: Sham Stimulation

Serious: 0/9 (0%)

Deaths: 0/9

Open-Label Phase: Active tcVNS Following Active tcVNS

Serious: 0/7 (0%)

Deaths: 0/7

Open-Label Phase: Active tcVNS Following Sham Stimulation

Serious: 0/8 (0%)

Deaths: 0/8

Other adverse events (8 terms — click to expand)

Reaction	System	Blinded Phase: Active tcVNS	Blinded Phase: Sham Stimul…	Open-Label Phase: Active t…	Open-Label Phase: Active t…
Palpitations	Cardiac disorders	—	—	—	—
Gastritis	Gastrointestinal disorders	—	—	—	—
Medical device site irritation	General disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Lymphocyte count increased	Investigations	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Skin irritation	Skin and subcutaneous tissue disorders	—	—	—	—

Data from ClinicalTrials.gov NCT05710640 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.