painful swollen joints
Conditions
Interventions
Patients who meet any of the following criteria are not to be enrolled in this
study:
* Inability to provide informed consent
* Significant psychiatric disease or substance abuse
* History of unilate
Sponsors
Setpoint Medical
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Adult-onset rheumatoid arthritis of at least six months duration as defined by the 2010 ACR/EULAR classification criteria (Aletaha, 2010) * Male or female patients, 18-75 years of age, inclusive * Functional status I, II, or III as classified according to the ACR 1991 revised criteria (Hochberg, 1992) * Patients must have active disease as defined by at least 4 active tender or swollen joints and CRP above 1.5 mg/dL, despite at least 3 months of treatment with methotrexate at a dose of up to 25 mg orally per week. * Patients may have been previously treated with TNF antagonists, but must have failed by reason of inadequate safety, intolerance to side effects, or development of antibodies (i.e., secondary failures), and specifically must not have failed due to lack of efficacy (i.e., primary failures, defined as non-responders after at least 16 weeks of treatment). Such patients must have had a washout period of at least 6 weeks for etanercept, and at least 12 weeks for infliximab, adalimumab, golimumab, or certolizumab pegol prior to enrollment. * At the discretion of the sponsor and the investigators, up to 2 of the patients enrolled may be patients who have failed both a TNF antagonist (either a primary or a secondary failure), AND have failed at least one other biological therapy having a non-TNF antagonist mechanism of action. Such patients may continue to use their current biologic therapy during the course of the study. * Patients must have normal Screening Visit studies. Patients with abnormal but clinically insignificant Screening Visit studies may be included after discussion with and approval by the sponsor*s medical monitor. * Women of childbearing potential must agree to use a double barrier method of contraception throughout the study
Exclusion criteria
Exclusion criteria: * Inability to provide informed consent * Significant psychiatric disease or substance abuse * History of unilateral or bilateral vagotomy * History of recurrent vaso-vagal syncope episodes * Known obstructive sleep apnea * Known history of cardiac rhythm disturbances, atrio-ventricular block of greater than first degree, or cardiac conduction pathway abnormalities other than isolated right bundle branch block or isolated left anterior fascicle block * Significant pharyngeal dysfunction or swallowing difficulties * Pre-existing clinically significant vocal cord damage or hoarseness * Previously implanted electrically active medical devices (e.g., cardiac pacemakers, automatic implantable cardioverter-defibrillators) * Asthma or chronic obstructive pulmonary disease not controlled by medications, or any other disease causing clinically significant dyspnea at time of screening * Active peptic ulcer disease * Intra-articular or parenteral corticosteroid treatment within 3 months of enrolment * Any investigational small molecule drug within 30 days of enrollment, or any investigational monoclonal antibody or investigational soluble receptor within 3 months of enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint * Change from Day 0 Visit to Day 42 Visit in DAS28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints * Percentage of patients who achieve ACR 20, 50, and 70 at Day 42 * Percentage of patients who achieve EULAR response and EULAR remission criteria at Day 42 * Change from Day 0 to Day 42 in EuroQoL EQ 5D instrument parameters * Change from Day 0 Visit to Day 42 Visit in Whole Blood Assay Biomarker LPS-inducible TNF release * Change from Day 0 Visit to Day 42 Visit in Serum Biomarkers * Change from Day 0 Visit to Day 42 Visit in Fluorescence-Activated Cell Sorter (FACS) Panel Biomarkers * Change from Day 0 Visit to Day 42 Visit in Synovial Biopsy cytokine and mediator protein expression by immunohistochemistry * Change from Day 0 to Day 42 in Synovial Biopsy cytokine gene expression by quantitative PCR Exploratory Endpoints * Changes in DAS28, ACR 20, 50, and 70 response rate, Serum Biomarkers, FACS Panel Biomarkers, and Whole Blood Assay Biomarkers during treatment withdrawal between Day 42 Visit and Day 56 Visit * Changes in DAS28, ACR 20, 50, and 70 response rate, Serum Biomarkers, FACS Panel Biomarkers, and Whole Blood Assay Biomarkers between Day 0 Visit and all visits other than Day 42 Safety Endpoints The following Safety Endpoints will be assessed at all time points following enrollment at the Implantation Visit: * Adverse Events * Serious Adverse Events * 12 Lead ECGs * Vital Signs * Safety Laboratory Studies | — |
Countries
Netherlands
Outcome results
None listed