taVNS in Veterans With Knee OA (AVAHCS)

NCT07804199 | Not Yet Recruiting FDA Device

• 2 other identifiers: RDX 26-0015150RX004845-02
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (5)

• Improvements in Clinical Pain (DVPRS)

  The DVPRS is a pain measurement tool used in the U.S. Military Health System and VA to assess pain intensity and impact on quality of life. It utilizes a numerical rating scale enhanced by words that describe function, sleep, activity, mood, and color-coding to enhance communication. Clinical pain, as measured by the Defense Veterans Pain Rating Scale (DVPRS), will be our primary outcome. This measure is rated on a scale of 0 to 10, with 0 being "no pain" and 10 being "as bad as it could be, nothing else matters". Assessments will be administered at the initial visit (week 1), 4-week follow-up visit, 12-week follow-up visit, and 6-month follow-up visit.

  Through study completion, average of 9 months

• Concentration of Pro-inflammatory Cytokines (Blood)

  Biomarker analysis (pro-inflammatory cytokines: TNF-α, IL-6, IL-1β) of blood samples, collected at baseline,1-month post-treatment, and 3 months post treatment. The hypothesis is that there will be an increase in anti-inflammatory mediators and decrease in pro-inflammatory cytokines with high-dose taVNS in comparison with the other groups, and that this will correlate with improved clinical outcomes. Specimens will be taken at the initial visit (week 1), 4-week follow-up visit, and 12-week follow-up visit.

  Through study completion, average of 9 months

• Concentration of Pro-inflammatory Cytokines (Synovial Fluid)

  Biomarker analysis (pro-inflammatory cytokines: TNF-α, IL-6, IL-1β; anti-inflammatory mediators: IL-10, TGF-β) of synovial fluid, collected at baseline,1-month post-treatment, and 3 months post treatment. The hypothesis is that there will be an increase in anti-inflammatory mediators and decrease in pro-inflammatory cytokines with high-dose taVNS in comparison with the other groups, and that this will correlate with improved clinical outcomes. Specimens will be taken at the initial visit (week 1), 4-week follow-up visit, and 12-week follow-up visit.

  Through study completion, average of 9 months

• Concentration of Anti-inflammatory Mediators (Blood)

  Biomarker analysis (anti-inflammatory mediators: IL-10, TGF-β) of blood samples, collected at baseline,1-month post-treatment, and 3 months post treatment. The hypothesis is that there will be an increase in anti-inflammatory mediators and decrease in pro-inflammatory cytokines with high-dose taVNS in comparison with the other groups, and that this will correlate with improved clinical outcomes. Specimens will be taken at the initial visit (week 1), 4-week follow-up visit, and 12-week follow-up visit.

  Through study completion, average of 9 months

• Concentration of Anti-inflammatory Mediators (Synovial Fluid)

  Biomarker analysis (anti-inflammatory mediators: IL-10, TGF-β) of synovial fluid and blood samples, collected at baseline,1-month post-treatment, and 3 months post treatment. The hypothesis is that there will be an increase in anti-inflammatory mediators and decrease in pro-inflammatory cytokines with high-dose taVNS in comparison with the other groups, and that this will correlate with improved clinical outcomes. Specimens will be taken at the initial visit (week 1), 4-week follow-up visit, and 12-week follow-up visit.

  Through study completion, average of 9 months

Secondary Outcomes (4)

• Changes in Pain Frequency and Intensity (PEG-3)

  Through study completion, average of 9 months

• Changes in Knee Pain, Function, and QOL (KOOS-12)

  Through study completion, average of 9 months

• Patient Reported Improvements (NIH-PROMIS)

  Through study completion, average of 9 months

• Treatment Prediction and Monitoring (Central Sensitization Inventory)

  Through study completion, average of 9 months

Study Arms (3)

Standard-of-care CSI

OTHER

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.

Drug: Methylprednisolone acetate

Low-dose taVNS

ACTIVE COMPARATOR

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.

Device: taVNS

High-dose taVNS

ACTIVE COMPARATOR

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.

Device: taVNS

Interventions

taVNS DEVICE

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.

Also known as: Nurosym

High-dose taVNS; Low-dose taVNS

Methylprednisolone acetate DRUG

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

Also known as: Depo-Medrol, Depo-Medrate, Depo-Medrone, gold-standard corticosteroid injection (CSI)

Standard-of-care CSI

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033-4004, United States

Location

Related Links

• Woodbury PAIN Lab Page

MeSH Terms

Conditions

Osteoarthritis, Knee; Pain

Interventions

Methylprednisolone Acetate; Methylprednisolone

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Anna Woodbury, MD

  Atlanta VA Medical and Rehab Center, Decatur, GA

  PRINCIPAL INVESTIGATOR

• Mercy A Udoji, MD

  Atlanta VA Medical and Rehab Center, Decatur, GA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Woodbury, MD

CONTACT

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

Anna M Ree, BA

CONTACT

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No masking for this project.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This 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. Clinical outcomes will be assessed at baseline, 1 month, and 3 months using validated tools for pain (Pain, Enjoyment of life, General activity (PEG-3), Defense and veterans Pain Rating Scale (DVPRS)) and function (Knee Injury and Osteoarthritis Outcome Score (KOOS), NIH Patient-Reported Outcomes Measurement Information System (PROMIS), and Central Sensitization Inventory). 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-).

Study Record Dates

• First Submitted: August 21, 2026
• First Posted: September 4, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: September 11, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)