Knee OsteoarthritistaVNSNCT07804199
taVNS in Veterans With Knee OA (AVAHCS)
A study testing Methylprednisolone acetate and taVNS in people with Knee Osteoarthritis, run by VA Office of Research and Development at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- Methylprednisolone acetate and taVNS
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Sep 2026to 1 Jan 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Atlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, 30033-4004
Anna Woodbury, MD, (404) 321-6111 ext. 6939, Anna.Woodbury@va.gov
Anna Woodbury, MD
About this study
Official title: Optimizing Home-Based Auricular Vagus Nerve Stimulation for Pain, Function, and Inflammation in Veterans With Knee Osteoarthritis: A Randomized Pilot Dose-Finding Study (AVAHCS) (F4845-C)
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.
Read the detailed description
This pilot study will be the first to test home-based taVNS against corticosteroid injections (CSI) in knee osteoarthritis (KOA) to assess their effects on pain, function, and serum/synovial fluid pro and anti-inflammatory biomarkers. Adult participants diagnosed clinically and/or radiographically with KOA (n=40) will be randomized to CSI (n=10) or 12 weeks of taVNS (high dose n=15; low dose n=15) and assessed pre-procedure and at 1- and 3-month timepoints. The following outcome measures will be assessed: PEG-3, DVPRS, NIH-PROMIS, KOOS, and Central Sensitization Inventory. In addition, biomarker levels in the serum and synovial fluid will be measured at baseline, 1- and 3-month timepoints.
This study will be the first to 1) directly compare taVNS against gold-standard CSI, 2) examine taVNS effects on cytokines in knee OA as compared to CSI, 3) target an ideal taVNS dosing strategy for knee OA, and 4) utilize Parasym , a home-based taVNS device previously shown to reduce heart failure symptoms and decrease TNF- 17 that has been classified as non-significant risk (NSR) by the FDA. The investigators are therefore testing a novel Veteran-centric, nonpharmacological intervention for knee OA; taVNS with Parasym offers a safe, self-administered alternative to opioids and invasive procedures, with minimal side effects and high potential for real-world implementation in the Veteran population.
Aim 1: Identify an ideal taVNS dosing regimen for analgesic effects. (30-60 minutes per day, 3 days per week 4,17 versus 1-2 hours per day, 7 days per week17 for 12 weeks) on clinical improvements in pain and function. Hypothesis for Aim 1: Pain (primary outcome), measured by the PEG-3 (3-item scale assessing pain intensity, interference with activity, and enjoyment of life)18 and DVPRS (assesses pain intensity + interference with activity, sleep, mood, stress)19 and function (secondary outcome) measured by the KOOS (Knee Injury and Osteoarthritis Outcome Score)20 and NIH PROMIS measures21 will be more improved in those undergoing high-dose taVNS (n=15) than vs. low-dose taVNS (n=15) or CSI (n=10). Central sensitization inventory will also be collected to evaluate it as a co-variate in predicting and monitoring treatment response.
Aim 2: Evaluate taVNS dose-dependent modulation of biomarkers associated with inflammation in Aim 1 participants. Synovial fluid and peripheral blood will be obtained pre-procedure and at 4- and 12-weeks following initiation of therapy. Hypothesis for Aim 2: taVNS results in greater reductions in pro-inflammatory cytokines (e.g., TNF- , IL-6, IL-1 ) and increased levels of anti-inflammatory mediators (e.g., IL-10, TGF- ) in synovial fluid and peripheral blood compared to CSI. The investigators expect that the higher dose group will demonstrate more pronounced changes in anti-inflammatory biomarkers as compared to low dose taVNS or CSI.
This study addresses a critical need for innovative, non-opioid OA therapies and supports the CReATE Motion Center's mission to advance regenerative therapies for Veterans. Based on results of this study, the investigators will choose the taVNS dosing strategy that best enhances clinical and anti-inflammatory effects. This pilot study has the potential to advance a novel, non-pharmacological approach to pain relief and functional recovery in a population with high unmet needs and is a critical first step to our understanding of dose optimization in taVNS for knee OA-related pain, function, and anti-inflammatory effects.
Our project is designed as a foundational step toward future combinatorial trials pairing taVNS with other therapies for chondroprotection.
- Conditions
- Knee Osteoarthritis
- Being tested
- Methylprednisolone acetate, taVNS
- Keywords
- Pain, Knee osteoarthritis, Biomarker analysis, Veterans, Transcutaneous auricular vagus nerve stimulation, Vagus nerve
- Medical subject headings
- Osteoarthritis, Knee, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylprednisolone acetateDrug
Also called Depo-Medrol, Depo-Medrate, Depo-Medrone, gold-standard corticosteroid injection (CSI)
FDA-approved injection treatment applied to the knee for purposes of KOA pain management.
taVNSDevice
Also called Nurosym
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Device: taVNS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through study completion, average of 9 months
Secondary outcomes (4)
Changes in Pain Frequency and Intensity (PEG-3)
The PEG is a 3-item patient-reported measure derived from the Brief Pain Inventory . It assesses average pain intensity, interference with enjoyment of life, and interference with general activity over the past week. Its minimally clinically important difference is 1-2 points. Assessments will be administered at the initial visit (week 1), 4-week follow-up visit, and 12-week follow-up visit.
Measured: Through study completion, average of 9 months
Changes in Knee Pain, Function, and QOL (KOOS-12)
The KOOS-12 is a 12-item scale that assesses knee pain, function, and quality of life (QOL). Items are rated on a 5-point scale (0=no problems, 4=extreme problems), summed, and converted to a 0-100 scale (0=severe problems, 100=no problems). The KOOS-12 evaluates pain frequency and intensity during common activities (i.e. walking on a flat surface, going up or down stairs, getting in and out of the car), offering a comprehensive view of limitations in activities of daily living (ADLs) attributable to knee pain. The MCID ranges from 14.2 to 21.9 points. Assessments will be administered at the initial visit (week 1), 4-week follow-up visit, and 12-week follow-up visit.
Measured: Through study completion, average of 9 months
Patient Reported Improvements (NIH-PROMIS)
NIH-PROMIS is a validated, 29-item patient-reported outcome measure assessing health-related quality of life (QOL) across seven domains: anxiety, depression, fatigue, pain interference, physical function, disturbance, and social participation, plus a single pain intensity item. Each domain has four items scored independently, mostly reflecting symptoms over the past seven days (except physical function which is not time bound). This instrument supports the generation of global physical and mental health summary scores, providing an overview of participants' quality of life. Scores are standardized as T-scores (mean 50; standard deviation 10) for ease of interpretation. Minimally important differences ranges from 2 to 6 points across domains, with values of 3 to 5 points commonly cited for pain interference and physical function in musculoskeletal conditions. Assessments will be administered at the initial visit (week 1), 4-week follow-up visit, and 12-week follow-up visit.
Measured: Through study completion, average of 9 months
Treatment Prediction and Monitoring (Central Sensitization Inventory)
Central sensitization inventory will also be collected to evaluate it as a co-variate in predicting and monitoring treatment response. Assessments will be administered at the initial visit (week 1), 4-week follow-up visit, and 12-week follow-up visit.
Measured: Through study completion, average of 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2026
- Study start29 Sep 2026
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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-).
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Anna Woodbury, MD, Principal investigator, Atlanta VA Medical and Rehab Center, Decatur, GAMercy A Udoji, MD, Principal investigator, Atlanta VA Medical and Rehab Center, Decatur, GA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07804199
- Sponsor's protocol ID
- RDX 26-001
- Other IDs
- 5150RX004845-02
- Acronym
- taVNS
- Status last verified
- Sep 2026
- First submitted
- 21 Aug 2026
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimizing Home-Based Auricular Vagus Nerve Stimulation for Pain, Function, and Inflammation in Veterans With Knee Osteoarthritis: A Randomized Pilot Dose-Finding Study (AVAHCS) (F4845-C)
- ClinicalTrials.gov ID
- NCT07804199
- Acronym / sponsor ID
- taVNS / RDX 26-001
- Conditions
- Knee Osteoarthritis
- Keywords
- Pain, Knee osteoarthritis, Biomarker analysis, Veterans, Transcutaneous auricular vagus nerve stimulation, Vagus nerve
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 29 Sep 2026 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 4 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This pilot study will be the first to test home-based taVNS against corticosteroid injections (CSI) in knee osteoarthritis (KOA) to assess their effects on pain, function, and serum/synovial fluid pro and anti-inflammatory biomarkers. Adult participants diagnosed clinically and/or radiographically with KOA (n=40) will be randomized to CSI (n=10) or 12 weeks of taVNS (high dose n=15; low dose n=15) and assessed pre-procedure and at 1- and 3-month timepoints. The following outcome measures will be assessed: PEG-3, DVPRS, NIH-PROMIS, KOOS, and Central Sensitization Inventory. In addition, biomarker levels in the serum and synovial fluid will be measured at baseline, 1- and 3-month timepoints.
This study will be the first to 1) directly compare taVNS against gold-standard CSI, 2) examine taVNS effects on cytokines in knee OA as compared to CSI, 3) target an ideal taVNS dosing strategy for knee OA, and 4) utilize Parasym , a home-based taVNS device previously shown to reduce heart failure symptoms and decrease TNF- 17 that has been classified as non-significant risk (NSR) by the FDA. The investigators are therefore testing a novel Veteran-centric, nonpharmacological intervention for knee OA; taVNS with Parasym offers a safe, self-administered alternative to opioids and invasive procedures, with minimal side effects and high potential for real-world implementation in the Veteran population.
Aim 1: Identify an ideal taVNS dosing regimen for analgesic effects. (30-60 minutes per day, 3 days per week 4,17 versus 1-2 hours per day, 7 days per week17 for 12 weeks) on clinical improvements in pain and function. Hypothesis for Aim 1: Pain (primary outcome), measured by the PEG-3 (3-item scale assessing pain intensity, interference with activity, and enjoyment of life)18 and DVPRS (assesses pain intensity + interference with activity, sleep, mood, stress)19 and function (secondary outcome) measured by the KOOS (Knee Injury and Osteoarthritis Outcome Score)20 and NIH PROMIS measures21 will be more improved in those undergoing high-dose taVNS (n=15) than vs. low-dose taVNS (n=15) or CSI (n=10). Central sensitization inventory will also be collected to evaluate it as a co-variate in predicting and monitoring treatment response.
Aim 2: Evaluate taVNS dose-dependent modulation of biomarkers associated with inflammation in Aim 1 participants. Synovial fluid and peripheral blood will be obtained pre-procedure and at 4- and 12-weeks following initiation of therapy. Hypothesis for Aim 2: taVNS results in greater reductions in pro-inflammatory cytokines (e.g., TNF- , IL-6, IL-1 ) and increased levels of anti-inflammatory mediators (e.g., IL-10, TGF- ) in synovial fluid and peripheral blood compared to CSI. The investigators expect that the higher dose group will demonstrate more pronounced changes in anti-inflammatory biomarkers as compared to low dose taVNS or CSI.
This study addresses a critical need for innovative, non-opioid OA therapies and supports the CReATE Motion Center's mission to advance regenerative therapies for Veterans. Based on results of this study, the investigators will choose the taVNS dosing strategy that best enhances clinical and anti-inflammatory effects. This pilot study has the potential to advance a novel, non-pharmacological approach to pain relief and functional recovery in a population with high unmet needs and is a critical first step to our understanding of dose optimization in taVNS for knee OA-related pain, function, and anti-inflammatory effects.
Our project is designed as a foundational step toward future combinatorial trials pairing taVNS with other therapies for chondroprotection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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-).
| Arm | Type | Receives |
|---|---|---|
| Standard-of-care CSI | Other | Drug: Methylprednisolone acetateParticipants allotted to this group will receive gold-standard corticosteroid injection (CSI), a standard-of-care option for treating and managing knee osteoarthritis (KOA) pain. |
| Low-dose taVNS | Active comparator | Device: taVNSTranscutaneous 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. |
| High-dose taVNS | Active comparator | Device: taVNSTranscutaneous 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. |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- 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:
- Severe comorbidities (e.g., uncontrolled liver/kidney disease, active malignancy, uncontrolled hypertension or cardiovascular disease, uncontrolled diabetes with neuropathy)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylprednisolone acetateAlso: Depo-Medrol, Depo-Medrate, Depo-Medrone, gold-standard corticosteroid injection (CSI)FDA-approved injection treatment applied to the knee for purposes of KOA pain management. | Drug | Standard-of-care CSI |
| taVNSAlso: NurosymTranscutaneous 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. | Device | High-dose taVNS, Low-dose taVNS |
Primary outcome
Improvements in Clinical Pain (DVPRS)
Time frame: Through study completion, average of 9 months
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.
Concentration of Pro-inflammatory Cytokines (Blood)
Time frame: Through study completion, average of 9 months
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.
Concentration of Pro-inflammatory Cytokines (Synovial Fluid)
Time frame: Through study completion, average of 9 months
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.
Concentration of Anti-inflammatory Mediators (Blood)
Time frame: Through study completion, average of 9 months
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.
Concentration of Anti-inflammatory Mediators (Synovial Fluid)
Time frame: Through study completion, average of 9 months
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.
4 secondary outcomes
Changes in Pain Frequency and Intensity (PEG-3)
Time frame: Through study completion, average of 9 months
Changes in Knee Pain, Function, and QOL (KOOS-12)
Time frame: Through study completion, average of 9 months
Patient Reported Improvements (NIH-PROMIS)
Time frame: Through study completion, average of 9 months
Treatment Prediction and Monitoring (Central Sensitization Inventory)
Time frame: Through study completion, average of 9 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Woodbury PAIN Lab PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anna Woodbury, MD principal investigator
Atlanta VA Medical and Rehab Center, Decatur, GA
Mercy A Udoji, MD principal investigator
Atlanta VA Medical and Rehab Center, Decatur, GA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Methylprednisolone acetate and taVNS in people with Knee Osteoarthritis, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anna Woodbury, MD ((404) 321-6111 ext. 6939, Anna.Woodbury@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvements in Clinical Pain (DVPRS) (time frame: Through study completion, average of 9 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.