Juvenile Idiopathic Arthritis (JIA)Phase 2AJA01NCT05710640
Transcutaneous Cervical Vagus Nerve Stimulation (tcVNS) in JIA
A Phase 2 study testing Active tcVNS in people with Juvenile Idiopathic Arthritis (JIA), run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 18 years
- Conditions the study is for
- Juvenile Idiopathic Arthritis (JIA)
- What is being tested?
- Active tcVNS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 7 sitesUnited States
- Study dates
- 27 Jun 2023to 15 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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:
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- 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:
- stable dose for at least 1 week prior to screening:
- Oral steroids, <= 0.2 mg/kg/day with a maximum 10 mg/day dose
- stable dose for at least 2 weeks prior to screening:
- NSAIDs
- stable dose for at least 8 weeks prior to screening:
- adalimumab
- anakinra
- canakinumab
- certolizumab pegol
- etanercept
- golimumab
- infliximab
- leflunomide
- methotrexate
- tocilizumab
- stable dose for at least 12 weeks prior to screening:
- abatacept
- If a female of child-bearing potential, the participant has a negative urine pregnancy test at screening
- If of reproductive potential, must agree to abstinence or effective methods of birth control for the duration of the study
Who cannot join
- 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
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- 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
- At any time previously without documented B cell repletion
- Participant has a comorbid disease that has required treatment with corticosteroids within the past year.
- Participant has an implantable electronic device such as a pacemaker, defibrillator, hearing aid, cochlear implant, insulin pump or deep brain stimulator.
- Participant has used cutaneous vagus nerve stimulation within 12 weeks prior to screening.
- Participant has received a live attenuated viral vaccine within 28 days prior to screening or is expected to receive one during the study.
- Participant has any condition which, in the opinion of the investigator, would jeopardize the participant's safety following exposure to a study intervention.
- Participant has any past or current medical problems or findings from a physical examination or laboratory testing that are not listed above but which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or may impact the quality or interpretation of the data obtained from the study.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Indiana University Medical Center: Riley Hospital for Children Department of Pediatric Rheumatology
Indianapolis, Indiana, 46202
Feinstein Institutes for Medical Research, Cohen Children's Medical Center: Pediatric Rheumatology
Lake Success, New York, 11040
Stephen D. Hassenfield Children's Center at NYU Langone Health
New York, New York, 10016
Nemours Children's Health: Department of Pediatric Rheumatology
Orlando, Florida, 32827
Division of Pediatric Rheumatology at the University of Utah School of Medicine and Primary Children's Hospital
Salt Lake City, Utah, 84132
University of California San Francisco School of Medicine: Department of Pediatrics, Division of Pediatric Rheumatology
San Francisco, California, 94158
Seattle Children's Hospital: Rheumatology Clinic
Seattle, Washington, 98105
About this study
Official title: Using the Cholinergic Anti-Inflammatory Pathway to Treat Juvenile Idiopathic Arthritis (AJA01)
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.
Read the detailed description
AJA01 is a multicenter, double-blind, sham-controlled, 16-week trial to evaluate the safety and effectiveness of tcVNS for the treatment of JIA.
A total of 100 participants will be randomized 1:1 to treatment with active tcVNS at the cymba concha or sham stimulation at the neck for 5 minutes once a day for 8 weeks. During this time, participants/parents, and participant assessors will be blinded to treatment assignment; treatments on clinic visit days will be conducted in the clinic under the supervision of a trained, unblinded staff member, and participants will only discuss the stimulation procedure with this staff member. An unblinded site investigator will follow up on any safety events. The double-blind, sham-controlled 8-week period will be followed by an 8-week open-label period in which all participants will receive treatment with active tcVNS at the cymba concha once a day for 5 minutes. Participants and their parents will be told it is likely they will feel the stimulation, but it should not be painful.
There are 10 visits for the study, 8 clinic visits and 2 tele-visits. Participants will have physical exams with joint assessments, lab tests, and questionnaire completion by the physicians and participants at each clinic visit. Participants will be trained by the unblinded coordinator to perform stimulation during the clinic visit following the randomization. Participants will perform the stimulation at home for 5 minutes daily. Participants will complete a diary to document the daily stimulation.
- Conditions
- Juvenile Idiopathic Arthritis (JIA)
- Being tested
- Active tcVNS, Sham tcVNS
- Keywords
- Juvenile Idiopathic Arthritis, JIA, Children, tcVNS, Cytokines, Inflammation, Nonsignificant risk, NSR
- Medical subject headings
- Arthritis, Juvenile, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active tcVNSDevice
Also called tVNS, Active tVNS, taVNS, Active taVNS
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.
Sham tcVNSDevice
Also called tVNS, Sham tVNS, taVNS, Sham taVNS
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.
Active tcVNSDevice
Also called tVNS, Active tVNS, taVNS, Active taVNS
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.
| Study group | Role | What they receive |
|---|---|---|
| Blinded phase | Experimental | Participants will receive 5 minutes of active tcVNS or sham tcVNS daily for 8 weeks. Receives: 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. Receives: Device: Active tcVNS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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 any visit are imputed as JIA ACR 50 non-responders at that visit.
Measured: 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
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 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 any visit are imputed as JIA ACR 30 non-responders at that visit.
Measured: 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
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 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 any visit are imputed as JIA ACR 70 non-responders at that visit.
Measured: 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
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, and ankles. This provides a score in the range of 0-57 with higher scores indicating worse disease activity. A negative change from Baseline signifies improvement.
Measured: 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
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 than 1 variable worsens by >30%. A negative change from Week 8 in any of the core set variables signifies improvement. Participants missing any of the JIA ACR core criteria at any visit are imputed as JIA ACR 50 non-responders at that visit.
Measured: Week 12 and 16
Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Responders at Weeks 12 and 16 Compared to Week 8
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 than 1 variable worsens by >30%. A negative change from Week 8 in any of the core set variables signifies improvement. Participants missing any of the JIA ACR core criteria at any visit are imputed as JIA ACR 30 non-responders at that visit.
Measured: At Weeks 12 and 16
Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Responders at Week 12 and 16 Compared to Week 8
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 than 1 variable worsens by >30%. A negative change from Week 8 in any of the core set variables signifies improvement. Participants missing any of the JIA ACR core criteria at any visit are imputed as JIA ACR 70 non-responders at that visit.
Measured: Weeks 12 and 16
Change From Week 8 in Juvenile Arthritis Disease Activity Score in 27 Joints (JADAS-27)
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 ankles. This provides a score in the range of 0-57 with higher scores indicating worse disease activity. A negative change from Week 8 signifies improvement.
Measured: Weeks 12 and 16
Longitudinal Trends From Baseline to Week 16 in Juvenile Arthritis Disease Activity Score in 27 Joints (JADAS-27)
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 ankles. This provides a score in the range of 0-57 with higher scores indicating worse disease activity.
Measured: Baseline; Weeks 4, 8, 12, 16
Number of Participants With a Treatment-emergent Adverse Event From 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 the middle ear
- Grade 1 or higher JIA flares
- All other Grade 2 and higher AEs
Measured: Day 0 to Week 8
Number of Participants With a Treatment-emergent Adverse Event From 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
- All other Grade 2 and higher AEs
Measured: Week 8 to Week 16
Number of Participants With a Treatment-emergent Serious Adverse Event From Day 0 to Week 8
A participant who experienced any serious 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.
Measured: Day 0 to Week 8
Number of Participants With a Treatment-emergent Serious Adverse Event From Week 8 to Week 16
A participant who experienced any serious untoward or unfavorable medical occurrence(s) associated with the investigational device or any study mandated procedures between Week 8 and Week 16.
Measured: Week 8 to Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2023
- Study start27 Jun 2023
- Primary completion13 Nov 2024
- Study completion15 Jan 2025
Why it stopped: Study was terminated due to feasibility concerns and budget constraints.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Juvenile Idiopathic Arthritis (JIA)Studies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Autoimmunity Centers of Excellence, Northwell Health
- Responsible party
- Sponsor
- Investigators
- Beth Gottlieb, MD, Study chair, Feinstein Institutes for Medical Research, Cohen Children's Medical Center: Pediatric RheumatologyCynthia Aranow, MD, Study chair, Northwell HealthTimir Datta-Chaudhuri, PhD, Study chair, Northwell HealthBetty Diamond, MD, Study chair, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05710640
- Sponsor's protocol ID
- DAIT AJA01
- Acronym
- AJA01
- Status last verified
- Nov 2025
- First submitted
- 12 Jan 2023
- Last updated
- 25 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: The plan is to share data upon completion of the study in the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from the Division of Allergy Immunology and Transplantation-funded grants and contracts.
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using the Cholinergic Anti-Inflammatory Pathway to Treat Juvenile Idiopathic Arthritis (AJA01)
- ClinicalTrials.gov ID
- NCT05710640
- Acronym / sponsor ID
- AJA01 / DAIT AJA01
- Conditions
- Juvenile Idiopathic Arthritis (JIA)
- Keywords
- Juvenile Idiopathic Arthritis, JIA, Children, tcVNS, Cytokines, Inflammation, Nonsignificant risk, NSR
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to feasibility concerns and budget constraints.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Autoimmunity Centers of Excellence, Northwell Health
- Study start
- 27 Jun 2023 (actual)
- Primary completion
- 13 Nov 2024 (actual)
- Study completion
- 15 Jan 2025 (actual)
- First posted
- 2 Feb 2023 (actual)
- Results
- Posted 25 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
AJA01 is a multicenter, double-blind, sham-controlled, 16-week trial to evaluate the safety and effectiveness of tcVNS for the treatment of JIA.
A total of 100 participants will be randomized 1:1 to treatment with active tcVNS at the cymba concha or sham stimulation at the neck for 5 minutes once a day for 8 weeks. During this time, participants/parents, and participant assessors will be blinded to treatment assignment; treatments on clinic visit days will be conducted in the clinic under the supervision of a trained, unblinded staff member, and participants will only discuss the stimulation procedure with this staff member. An unblinded site investigator will follow up on any safety events. The double-blind, sham-controlled 8-week period will be followed by an 8-week open-label period in which all participants will receive treatment with active tcVNS at the cymba concha once a day for 5 minutes. Participants and their parents will be told it is likely they will feel the stimulation, but it should not be painful.
There are 10 visits for the study, 8 clinic visits and 2 tele-visits. Participants will have physical exams with joint assessments, lab tests, and questionnaire completion by the physicians and participants at each clinic visit. Participants will be trained by the unblinded coordinator to perform stimulation during the clinic visit following the randomization. Participants will perform the stimulation at home for 5 minutes daily. Participants will complete a diary to document the daily stimulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Blinded phase | Experimental | Device: Active tcVNS, Device: Sham tcVNSParticipants will receive 5 minutes of active tcVNS or sham tcVNS daily for 8 weeks. |
| Open-Label phase | Experimental | Device: Active tcVNSParticipants will receive 5 minutes of stimulation via the active tcVNS device for 8 weeks after a double-blind, sham-controlled 8- week period. |
Who may qualify
- Ages
- 5 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (34 listed)
- Participant is 5 through 18 years of age (inclusive) at screening.
- Regarding informed consent and compliance:
- 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:
- 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:
Key exclusion criteria (22 listed)
- Other than NSAIDs or intra-articular injections, participant has been treated for JIA with lack of efficacy with:
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active tcVNSAlso: tVNS, Active tVNS, taVNS, Active taVNSParticipants 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. | Device | Blinded phase |
| Sham tcVNSAlso: tVNS, Sham tVNS, taVNS, Sham taVNSParticipants 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. | Device | Blinded phase |
| Active tcVNSAlso: tVNS, Active tVNS, taVNS, Active taVNSParticipants 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. | Device | Open-Label phase |
Primary outcome
Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Responders at Week 8 Compared to Baseline
Time frame: 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 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.
13 secondary outcomes
Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Responders at Weeks 4, 12, and 16 Compared to Baseline
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Week 12 and 16
Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Responders at Weeks 12 and 16 Compared to Week 8
Time frame: At Weeks 12 and 16
Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Responders at Week 12 and 16 Compared to Week 8
Time frame: Weeks 12 and 16
Change From Week 8 in Juvenile Arthritis Disease Activity Score in 27 Joints (JADAS-27)
Time frame: Weeks 12 and 16
Longitudinal Trends From Baseline to Week 16 in Juvenile Arthritis Disease Activity Score in 27 Joints (JADAS-27)
Time frame: Baseline; Weeks 4, 8, 12, 16
Number of Participants With a Treatment-emergent Adverse Event From Day 0 to Week 8.
Time frame: Day 0 to Week 8
Number of Participants With a Treatment-emergent Adverse Event From Week 8 to Week 16
Time frame: Week 8 to Week 16
Number of Participants With a Treatment-emergent Serious Adverse Event From Day 0 to Week 8
Time frame: Day 0 to Week 8
Number of Participants With a Treatment-emergent Serious Adverse Event From Week 8 to Week 16
Time frame: Week 8 to Week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Autoimmunity Centers of Excellence (ACE)Link provided by the sponsor.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. The plan is to share data upon completion of the study in the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from the Division of Allergy Immunology and Transplantation-funded grants and contracts.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beth Gottlieb, MD study chair
Feinstein Institutes for Medical Research, Cohen Children's Medical Center: Pediatric Rheumatology
Cynthia Aranow, MD study chair
Northwell Health
Timir Datta-Chaudhuri, PhD study chair
Northwell Health
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Active tcVNS in people with Juvenile Idiopathic Arthritis (JIA), run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Responders at Week 8 Compared to Baseline (time frame: Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2025; AzTrials last refreshed its copy on 26 Oct 2026.