taVNS in Veterans With Knee OA (AVAHCS)

The objectives of this study are to identify an optimal transcutaneous auricular vagus nerve stimulation (taVNS) dosing regimen for pain relief and anti-inflammatory effects in Veterans with knee osteoarthritis (OA), compared to corticosteroid injection (CSI), and lay the groundwork for future combinatorial therapies with cell-based approaches. The population for this study is Veterans with osteoarthritis (OA). This single-center, randomized pilot study will enroll participants with knee OA, who will be allocated to CSI (n=10), high-dose taVNS (n=15; 1-2 hours/day, 7 days/week), or low-dose taVNS (n=15; 30-60 min/day, 3 days/week) for 12 weeks. Synovial fluid and blood samples will be collected at baseline, 4, and 12 weeks for biomarker analysis (pro-inflammatory cytokines: TNF-, IL-6, IL-1 ; anti-inflammatory mediators: IL-10, TGF-). The approximate study duration for each individual participant is 12 weeks of treatment with assessment visits at baseline, one month, and three months. Participants will be recruited at the Atlanta VA. The anticipated total enrollment is 40 participants. No specimens or data will be banked for future research use. Informed consent will be obtained from participants in person via signatures on written informed consent forms.

Inclusion Criteria: * Clinical diagnosis of knee osteoarthritis according to the American College of Rheumatology (ACR) criteria, confirmed by radiologic evidence of the same. * Moderate to severe knee pain, as assessed by the Defense Veterans Pain Rating Scale (DVPRS), a validated pain scale (score ≥4) * Willingness to discontinue current knee osteoarthritis (OA) pain medications (except permitted rescue medication such as acetaminophen/paracetamol) during the trial * Ability to provide informed consent and comply with all study procedures * Ambulatory and able to attend all study visits Exclusion Criteria: * History or evidence of inflammatory joint disease (e.g., rheumatoid arthritis, spondyloarthropathy), secondary or metabolic causes of arthritis, or significant trauma to the knee within 3 months prior to screening * Recent or planned major knee surgery on the index knee (arthroplasty or arthroscopy within 6 months) * Received intra-articular corticosteroid or hyaluronic acid injections in the index knee within 12 weeks prior to screening, or systemic corticosteroids within 30 days * Contraindications to transcutaneous auricular vagus nerve stimulation (taVNS), such as: oMetal implants above the neck oActive ear infection, recent ear trauma, or chronic ear/facial pain oPrior vagus nerve surgery (including vagotomy) or ongoing VNS therapy for another condition * Severe comorbidities (e.g., uncontrolled liver/kidney disease, active malignancy, uncontrolled hypertension or cardiovascular disease, uncontrolled diabetes with neuropathy) * Participation in another interventional clinical trial within the past 2 months * Inability to provide informed consent or comply with protocol requirements (e.g., significant cognitive impairment) * Any unstable or severe psychiatric disorder that, in the investigator's opinion, would compromise safety or compliance