Using the Cholinergic Anti-Inflammatory Pathway to Treat Juvenile Idiopathic Arthritis (AJA01)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Juvenile Idiopathic Arthritis (JIA)
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 18
- Locations
- 7
- Primary Endpoint
- Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Responders at Week 8 Compared to Baseline
- Status
- Terminated
- Last Updated
- 5 months ago
Overview
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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).
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Number of Participants With a Treatment-emergent Serious Adverse Event From Week 8 to Week 16(Week 8 to Week 16)
- 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)
- Proportion of Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Responders at Weeks 12 and 16 Compared to Week 8(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(Weeks 12 and 16)
- Change From Week 8 in Juvenile Arthritis Disease Activity Score in 27 Joints (JADAS-27)(Weeks 12 and 16)
- Longitudinal Trends From Baseline to Week 16 in Juvenile Arthritis Disease Activity Score in 27 Joints (JADAS-27)(Baseline; Weeks 4, 8, 12, 16)
- Number of Participants With a Treatment-emergent Adverse Event From Day 0 to Week 8.(Day 0 to Week 8)
- Number of Participants With a Treatment-emergent Adverse Event From Week 8 to Week 16(Week 8 to Week 16)
- Number of Participants With a Treatment-emergent Serious Adverse Event From Day 0 to Week 8(Day 0 to Week 8)