Recruiting

taVNS & CSI

Sponsor:

VA Office of Research and Development

Code:

NCT07804199

Conditions

Knee Osteoarthritis

Eligibility Criteria

Sex: All

Age: 45 - 70+

Healthy Volunteers: Not accepted

Interventions

Methylprednisolone acetate

taVNS

Study Details

Brief summary:

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.

Conditions

Knee Osteoarthritis

Study ID

NCT07804199

Start date

Sep 29, 2026

Status verified date

Sep, 2026

Completion date

Jan 1, 2028

Anticipated

Primary completion date

Jan 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 45 - 70+

Healthy Volunteers: Not accepted

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:

  • Metal implants above the neck
  • Active ear infection, recent ear trauma, or chronic ear/facial pain
  • Prior vagus nerve surgery (including vagotomy) or ongoing vagus nerve stimulation (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

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Standard-of-care CSI

Participants allotted to this group will receive gold-standard corticosteroid injection (CSI), a standard-of-care option for treating and managing knee osteoarthritis (KOA) pain.

active comparator: Low-dose taVNS

Transcutaneous auricular vagus nerve stimulation (taVNS) is a self-administered, home-based, non-invasive therapy with minimal risk of side effects. Mechanistically, taVNS targets auricular vagal afferents and requires afferent signaling to the nucleus tractus solitarius (NTS) to activate downstream efferent pathways in the central nervous system, including higher brain regions involved in pain processing (Fig 1), exerting anti-nociceptive effects. Participants allocated to this group will receive low-dose taVNS (n=15; 30-60 min/day, 3 days/week) for 12 weeks.

active comparator: High-dose taVNS

Transcutaneous auricular vagus nerve stimulation (taVNS) is a self-administered, home-based, non-invasive therapy with minimal risk of side effects. Mechanistically, taVNS targets auricular vagal afferents and requires afferent signaling to the nucleus tractus solitarius (NTS) to activate downstream efferent pathways in the central nervous system, including higher brain regions involved in pain processing (Fig 1), exerting anti-nociceptive effects. Participants allocated to this group will receive high-dose taVNS (n=15; 1-2 hours/day, 7 days/week) for 12 weeks.

Interventions

Methylprednisolone acetate

FDA-approved injection treatment applied to the knee for purposes of KOA pain management.

taVNS

Transcutaneous auricular vagus nerve stimulation (taVNS) is a self-administered, home-based, non-invasive therapy with minimal risk of side effects. Mechanistically, taVNS targets auricular vagal afferents and requires afferent signaling to the nucleus tractus solitarius (NTS) to activate downstream efferent pathways in the central nervous system, including higher brain regions involved in pain processing (Fig 1), exerting anti-nociceptive effects.

Primary outcome measure

  • Improvements in Clinical Pain (DVPRS) [ Time Frame: Through study completion, average of 9 months ]
  • Concentration of Pro-inflammatory Cytokines (Blood) [ Time Frame: Through study completion, average of 9 months ]
  • Concentration of Pro-inflammatory Cytokines (Synovial Fluid) [ Time Frame: Through study completion, average of 9 months ]
  • Concentration of Anti-inflammatory Mediators (Blood) [ Time Frame: Through study completion, average of 9 months ]
  • Concentration of Anti-inflammatory Mediators (Synovial Fluid) [ Time Frame: Through study completion, average of 9 months ]

Central Contacts and Locations

Central contacts

Anna Woodbury, MD

(404) 321-6111Anna.Woodbury@va.gov

Anna M Ree, BA

(404) 321-6111anna.ree@va.gov

Locations

Atlanta VA Medical and Rehab Center, Decatur, GA

Recruiting

Decatur, Georgia, United States, 30033-4004

Contacts

Anna Woodbury, MD

(404) 321-6111Anna.Woodbury@va.gov

Principal Investigator:

Anna Woodbury, MD

More Information

Sponsor

VA Office of Research and Development

Last update posted

Oct 5, 2026

Last verified

Sep, 2026

Keywords

  • Pain
  • Knee osteoarthritis
  • Biomarker analysis
  • Veterans
  • Transcutaneous auricular vagus nerve stimulation
  • Vagus nerve

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-06. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-10-05. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.