Vagus Nerve Stimulation for Knee Osteoarthritis

Overseen By Kosaku Aoyagi, PT, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas, El Paso

Disqualifiers: Cardiac rhythm disturbances, Vagal syncope, Pacemaker, Serious diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Transcutaneous vagus nerve stimulation (tVNS) for knee osteoarthritis?

Research on similar conditions, like erosive hand osteoarthritis, shows that transcutaneous vagus nerve stimulation (tVNS) can reduce pain and inflammation. A pilot study found that tVNS significantly decreased hand pain and improved function, suggesting it might also help with knee osteoarthritis. ^{1 2 3 4 5}

Is vagus nerve stimulation safe for humans?

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally considered safe, with mild and temporary side effects like ear pain, headache, and tingling. Studies show no significant risk of severe adverse events compared to controls. ^{6 7 8 9 10}

How does transcutaneous vagus nerve stimulation (tVNS) differ from other treatments for knee osteoarthritis?

Transcutaneous vagus nerve stimulation (tVNS) is unique because it involves non-invasive electronic stimulation of the ear's auricular concha to potentially reduce pain, unlike other treatments that may involve medication or surgery. This method is being tested for its effectiveness in knee osteoarthritis, offering a novel approach that could complement existing therapies. ^{11 12 13 14 15}

What is the purpose of this trial?

The goal of this clinical trial is to test the feasibility and effectiveness of transcutaneous vagus nerve stimulation (tVNS) to the ear on pain and autonomic function in people with knee osteoarthritis (OA). The main questions it aims to answer are: 1) whether tVNS is feasible to be used in people with knee OA; 2) whether tVNS demonstrates the trend in improving knee pain; and 3) whether tVNS has physiological effects on autonomic function (e.g., parasympathetic function) and pain perception in the central nervous system such as brain (i.e., central pain mechanisms). Participants will be asked to complete a battery of self-reported questionnaires about their demographic and behavioral information, ethnicity, pain, sleep, psychological/emotional symptoms. Subsequently, participants will complete baseline assessment where investigators will assess their knee pain severity, central pain sensitivity, and heart rate variability (a measurement for autonomic function). Then participants will receive a 60-minute tVNS. Investigators will redo the same assessment as baseline assessment after tVNS intervention to see the degree of knee pain, central pain sensitivity, and autonomic function changes. At the end of the study, investigators will assess their satisfaction level with the tVNS intervention and the feasibility of the intervention (e.g., completion rate, side effects).

Eligibility Criteria

This trial is for adults over 45 with chronic knee pain from osteoarthritis, experiencing an average pain intensity of 4 or higher on a scale of 0 to 10. Participants should have had this pain for at least three months and be able to communicate in English.

Inclusion Criteria

My main health issue is knee pain.

Able to understand English

I have had knee pain for at least 3 months.

Exclusion Criteria

Use of other medical devices electrically active (pacemaker, transcutaneous electrical nerve stimulation, etc.)

I have not had any treatments for knee pain in the last 3 months.

Pregnant or breastfeeding woman

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete self-reported questionnaires and baseline assessments of knee pain severity, central pain sensitivity, and heart rate variability.

1 day

1 visit (in-person)

tVNS Intervention

Participants receive a 60-minute transcutaneous vagus nerve stimulation (tVNS) session at the cymba concha of the left ear.

1 day

1 visit (in-person)

Post-Intervention Assessment

Investigators assess changes in knee pain, central pain sensitivity, and autonomic function immediately after and 15 minutes after tVNS intervention.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including satisfaction level and safety assessment.

1-2 weeks

Treatment Details

Interventions

• Transcutaneous vagus nerve stimulation

Trial Overview The study tests if ear-based vagus nerve stimulation (tVNS) can reduce knee pain and affect the body's autonomic functions like heart rate variability in people with knee osteoarthritis. It checks tVNS's feasibility, its impact on central nervous system pain mechanisms, and overall satisfaction with the treatment.

Participant Groups

Group I: tVNS group Experimental Treatment 1 Intervention

This will be a single-arm study where all study participants will receive transcutaneous vagus nerve stimulation (tVNS) at the cymba concha of the left ear for 60 minutes. The tVNS parameters will be a below-discomfort-threshold intensity with 25 Hz and a pulse width of 250 uS.

Who Is Running the Clinical Trial?

University of Texas, El Paso

Lead Sponsor

Trials

17

Recruited

3,000+

Findings from Research

The ESTIVAL Study is a randomized, double-blind, sham-controlled trial designed to evaluate the safety and efficacy of transcutaneous vagus nerve stimulation (tVNS) in patients with erosive hand osteoarthritis, involving 156 participants across 18 hospital centers in France.

The primary outcome will measure changes in self-reported hand pain over 12 weeks, with secondary outcomes assessing function, quality of life, and biomarkers, aiming to provide insights into the potential benefits of tVNS for managing pain and inflammation in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation in erosive hand osteoarthritis: protocol for the randomised, double-blind, sham-controlled ESTIVAL trial. Courties, A., Deprouw, C., Rousseau, A., et al.[2022]

In an open-label pilot study involving 18 patients with erosive hand osteoarthritis, transcutaneous auricular VNS (taVNS) significantly reduced hand pain by a median of 23.5 mm on a pain scale after 4 weeks, indicating its potential efficacy in managing symptoms.

The study found that taVNS was well-tolerated, with no serious adverse events reported, suggesting it is a safe intervention for patients, although one participant experienced discomfort leading to discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Transcutaneous Vagus Nerve Stimulation in Erosive Hand Osteoarthritis: Results from a Pilot Trial. Courties, A., Deprouw, C., Maheu, E., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) significantly reduced postural tachycardia in patients with POTS, showing a mean heart rate increase of 17.6 beats/min in the active group compared to 31.7 beats/min in the sham group after 2 months.

tVNS also led to lower levels of antiadrenergic autoantibodies and inflammatory cytokines, along with improved heart rate variability, indicating its potential as a safe and effective noninvasive treatment for POTS without any reported side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial. Stavrakis, S., Chakraborty, P., Farhat, K., et al.[2023]

Transauricular vagus nerve stimulation (taVNS) significantly reduced the incidence of delayed neurocognitive recovery (dNCR) in elderly patients after total joint arthroplasty, with only 10% of the taVNS group experiencing dNCR compared to 27.1% in the sham stimulation group.

The reduction in dNCR was associated with lower levels of inflammatory markers and cholinesterase activity in the taVNS group, suggesting that taVNS may help mitigate inflammation and brain damage following surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of transcutaneous auricular vagus nerve stimulation on delayed neurocognitive recovery in elderly patients. Zhou, Q., Yu, L., Yin, C., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) was found to be feasible and safe for patients with persistent impairment of consciousness after severe traumatic brain injury (TBI), with minimal side effects reported during an eight-week treatment period.

Out of five patients treated, three showed significant improvements in consciousness as measured by the Coma Recovery Scale-Revised (CRS-R), suggesting that tVNS may have potential benefits for recovery following severe TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagus Nerve Stimulation in Patients With Severe Traumatic Brain Injury: A Feasibility Trial. Hakon, J., Moghiseh, M., Poulsen, I., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Transcutaneous vagus nerve stimulation (tVNS) significantly improves cardiac baroreflex sensitivity (cBRS) and autonomic modulation in healthy young men, as shown in a study with 13 participants.

The study effectively controlled for placebo effects by using two sham protocols, confirming that the observed benefits were specific to the stimulation of the auricular branch of the vagus nerve.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial. Antonino, D., Teixeira, AL., Maia-Lopes, PM., et al.[2018]

Transcutaneous auricular vagus nerve stimulation (TaVNS) effectively normalized gastric dysrhythmias in healthy individuals during a water-load test, indicating its potential as a treatment for gastric symptoms.

The study found that TaVNS at 40 Hz improved heart rate variability and reduced bloating, suggesting it positively influences both parasympathetic and sympathetic nervous system pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. Du, P., Maharjan, A., Calder, S., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improves depression symptoms, as evidenced by reduced scores on the Hamilton Depression Scale in a review of 12 studies involving 838 participants.

taVNS shows comparable response rates to traditional antidepressants and has fewer side effects, suggesting it could be a safe alternative or complementary treatment for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. Tan, C., Qiao, M., Ma, Y., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

This trial will evaluate the efficacy of transcutaneous vagal stimulation (TVS) in reducing pain for 70 participants aged 55 and older with knee osteoarthritis (KOA), alongside a structured exercise program over four weeks.

If effective, TVS could become a new therapeutic option for managing pain in KOA, potentially enhancing current treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagal Stimulation in Knee Osteoarthritis (TRAVKO): Protocol of a Superiority, Outcome Assessor- and Participant-Blind, Randomised Controlled Trial. Bascour-Sandoval, C., Gajardo-Burgos, R., Muñoz-Poblete, C., et al.[2023]

In a study involving 34 subjects with knee osteoarthritis, transcutaneous electrical nerve stimulation (TENS) at frequencies of 2 Hz, 100 Hz, or alternating between both significantly reduced pain and improved mobility compared to a placebo.

All active TENS treatments showed similar efficacy in reducing pain and enhancing knee range of motion, indicating that the specific frequency may not be as critical as previously thought for pain relief in osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal stimulation frequency of transcutaneous electrical nerve stimulation on people with knee osteoarthritis. Law, PP., Cheing, GL.[2022]

Transcutaneous electrical nerve stimulation (TENS) significantly reduces pain in patients with knee osteoarthritis, with a strong effect size based on a meta-analysis of 14 trials.

However, TENS did not show a significant difference in overall function or discontinuation rates compared to control groups, suggesting that while it is effective for pain relief, its impact on overall knee function may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Nerve Stimulation in Patients With Knee Osteoarthritis: Evidence From Randomized-controlled Trials. Chen, LX., Zhou, ZR., Li, YL., et al.[2019]

The study aimed to assess the effectiveness of a new transcutaneous electrical nerve stimulation (TENS) device for treating knee osteoarthritis compared to standard nonoperative treatments.

This research highlights TENS as a promising non-surgical option for managing osteoarthritis symptoms, potentially offering patients an alternative to more invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Knee Osteoarthritis: Does Transcutaneous Electrical Nerve Stimulation Work? Cherian, JJ., Kapadia, BH., McElroy, MJ., et al.[2018]

In a case report involving three patients with knee osteoarthritis who were unable or unwilling to have knee surgery, temporary peripheral nerve stimulation (PNS) was used as a treatment.

Two out of the three patients experienced significant pain reduction and improved functioning, suggesting that temporary PNS could be a safe and effective alternative for managing chronic knee pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Report of Three Patients Who Underwent Temporary Peripheral Nerve Stimulation for Treatment of Knee Pain Secondary to Osteoarthritis. Zhu, CC., Gargya, A., Haider, N.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation in erosive hand osteoarthritis: protocol for the randomised, double-blind, sham-controlled ESTIVAL trial. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Transcutaneous Vagus Nerve Stimulation in Erosive Hand Osteoarthritis: Results from a Pilot Trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Effect of transcutaneous auricular vagus nerve stimulation on delayed neurocognitive recovery in elderly patients. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagus Nerve Stimulation in Patients With Severe Traumatic Brain Injury: A Feasibility Trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagal Stimulation in Knee Osteoarthritis (TRAVKO): Protocol of a Superiority, Outcome Assessor- and Participant-Blind, Randomised Controlled Trial. [2023]

12. Sweden pubmed.ncbi.nlm.nih.gov

Optimal stimulation frequency of transcutaneous electrical nerve stimulation on people with knee osteoarthritis. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Nerve Stimulation in Patients With Knee Osteoarthritis: Evidence From Randomized-controlled Trials. [2019]

14. United States pubmed.ncbi.nlm.nih.gov

Knee Osteoarthritis: Does Transcutaneous Electrical Nerve Stimulation Work? [2018]

15. United States pubmed.ncbi.nlm.nih.gov

A Case Report of Three Patients Who Underwent Temporary Peripheral Nerve Stimulation for Treatment of Knee Pain Secondary to Osteoarthritis. [2023]