Non-Invasive Vagus Nerve Stimulation for Stroke Recovery

(NOVIS Trial)

Overseen By Rachel Markley, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Methodist Hospital Research Institute

Disqualifiers: Severe psychiatric illnesses, Bilateral paresis, Severe uncontrolled medical problems, Pregnancy, Others

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

Compensation: Varies

Number of Visits: 12

Duration: 6 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to aid stroke recovery using non-invasive vagus nerve stimulation (taVNS). Researchers aim to determine if this gentle electrical treatment can improve motor function post-stroke. Participants are divided into two groups: one receives the actual treatment, while the other receives a sham (placebo-like) version. The trial seeks individuals who have experienced a stroke, still have weakness on one side of their body, and can follow basic commands. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance stroke recovery methods.

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's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this non-invasive VNS is safe for stroke recovery?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe. Studies have found that taVNS can improve movement in stroke patients without causing noticeable side effects. Most side effects, if they occur, are mild and temporary, such as slight skin irritation or tingling.

Overall, taVNS is considered a safe method with only minor issues reported by patients, making it a promising option for those seeking to support their recovery from a stroke. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about non-invasive vagus nerve stimulation (taVNS) for stroke recovery because it offers a unique approach compared to traditional treatments like physical therapy and medications. Unlike these standard options, which often focus on physical rehabilitation or managing symptoms, taVNS targets the vagus nerve with a gentle electrical current to potentially enhance brain plasticity and improve motor function. This method is non-invasive, meaning it doesn't require surgery, and it could lead to faster and more effective recovery by directly engaging the nervous system in a novel way.

What evidence suggests that this non-invasive VNS is effective for stroke recovery?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS), a treatment available to participants in this trial, can aid stroke recovery. Specifically, taVNS improves arm and hand movement in stroke patients. Studies suggest its effectiveness is comparable to other types of vagus nerve stimulation. Long-term results indicate that combining taVNS with standard rehabilitation significantly enhances recovery of movement and sensation. Additionally, taVNS effectively reduces post-stroke depression when paired with regular therapy. Overall, these findings support taVNS as a promising treatment option for improving stroke recovery. ^{3 4 5 6 7}

Who Is on the Research Team?

Timea Hodics, MD

Principal Investigator

The Methodist Hospital Research Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 who had a stroke at least 6 months ago and have some movement limitations but can follow simple commands. It's open to all races and genders. People with severe muscle stiffness or those who cannot safely receive non-invasive VNS therapy are excluded.

Inclusion Criteria

I am over 18 years old.

I had a stroke that caused weakness on one side of my body.

I can move my shoulder, elbow, wrist, and hand normally.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive non-invasive trans-auricular vagus nerve stimulation (taVNS) during occupational therapy for motor recovery

6 weeks

Weekly sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Post intervention assessments at week 12 and week 18

Open-label extension

Participants in the sham group may receive active taVNS in a cross-over phase to assess sustained clinical improvement

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• taVNS

Trial Overview The study tests the safety and effectiveness of non-invasive vagus nerve stimulation (taVNS) as a treatment to improve recovery after a stroke. Participants will undergo taVNS therapy to see if it helps in regaining motor functions.

How Is the Trial Designed?

Group I: taVNS Experimental Treatment 1 Intervention

Weak current (up to 0.8-4 mA) will be delivered using pulses according to standard protocol during each motor task for up to 90-minutes through surface electrodes which will be administered using the intensity identified as resulting in well tolerated skin sensation and best motor performance during our initial testing session.

Group II: Sham Stimulation Placebo Group 1 Intervention

Same procedure as with the active stimulation using the device's sham settings to elicit the same cutaneous sensation as the other stimulation conditions..

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Published Research Related to This Trial

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising non-invasive treatment that can effectively improve motor function in patients who have experienced a stroke.

This review highlights the importance of stimulation parameters and timing, as well as the development of new devices, to enhance the application of taVNS in rehabilitating upper limb motor dysfunction after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Research Progress of the Post-Stroke Upper Limb Motor Function Improvement via Transcutaneous Auricular Vagus Nerve Stimulation. Shi, X., Zhao, J., Xu, S., et al.[2023]

Transcutaneous vagus nerve stimulation (tVNS) has shown potential in reducing infarct size in animal models of hyperacute stroke and enhancing neurological recovery in chronic stroke when paired with limb movements.

The review emphasizes the need for further research to better understand the mechanisms of tVNS and to effectively translate its benefits into clinical practice for both acute and chronic stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tVNS in Stroke: A Narrative Review on the Current State and the Future. Baig, SS., Kamarova, M., Bell, SM., et al.[2023]

Vagus nerve stimulation (VNS) combined with rehabilitation was found to be safe and feasible for improving arm function in stroke patients, with all participants completing the therapy despite some serious adverse events related to surgery.

At 90 days post-therapy, patients receiving active VNS showed a significant improvement in upper limb function compared to the control group, with an 88% clinically meaningful response rate, suggesting that VNS may enhance rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke. Kimberley, TJ., Pierce, D., Prudente, CN., et al.[2019]

In a study involving 12 chronic stroke patients, noninvasive transcutaneous auricular vagus nerve stimulation (taVNS) combined with repetitive motor practice showed potential to improve sensory recovery, with 64% of participants regaining some sensation after treatment.

The results suggest that taVNS may enhance sensory recovery alongside motor rehabilitation, but further research with a larger group is needed to fully understand its effects on overall functional recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation with Upper Limb Repetitive Task Practice May Improve Sensory Recovery in Chronic Stroke. Baig, SS., Falidas, K., Laud, PJ., et al.[2020]

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]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improved upper limb motor function in 21 subacute ischemic stroke patients compared to a sham treatment, as measured by the Fugl-Meyer assessment and other functional tests after 15 days of intervention.

The study found taVNS to be safe, with only one reported case of skin redness, indicating it may be a beneficial and low-risk option for enhancing recovery in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect and Safety of Transcutaneous Auricular Vagus Nerve Stimulation on Recovery of Upper Limb Motor Function in Subacute Ischemic Stroke Patients: A Randomized Pilot Study. Wu, D., Ma, J., Zhang, L., et al.[2021]

Non-invasive transcutaneous vagus nerve stimulation (tVNS) has shown promise in improving neurological recovery after stroke, potentially reducing infarct size and enhancing motor function through mechanisms like anti-inflammatory effects and neuroplasticity.

Pilot clinical trials suggest that auricular tVNS, when combined with rehabilitation, may significantly improve upper limb motor and sensory functions in chronic stroke patients, indicating its potential as a viable alternative to invasive vagus nerve stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation (tVNS) in stroke: the evidence, challenges and future directions. Baig, SS., Kamarova, M., Ali, A., 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]

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.123.043414

tVNS in Stroke: A Narrative Review on the Current State ... Transcutaneous vagus nerve stimulation (tVNS) has shown promising evidence as a tool to reduce infarct size in animal models of hyperacute stroke.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32802039/

Effect and Safety of Transcutaneous Auricular Vagus Nerve ... This study revealed that taVNS appeared to be beneficial to the recovery of upper limb motor function in subacute ischemia stroke patients without obvious ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05943431

taVNS Paired With Motor Training for Upper-extremity ... A recent meta-analysis has shown that the efficacy of taVNS in upper extremity rehabilitation for stroke patients can be comparable to that of VNS. Therefore, ...

4. journals.lww.com journals.lww.com/nrronline/fulltext/2022/08000/efficacy_and_safety_of_transcutaneous_auricular.37.aspx

Efficacy and safety of transcutaneous auricular vagus ... The follow-up results over 1 year revealed that ta-VNS combined with conventional rehabilitation training greatly improved the recovery of motor and sensory ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724004191

Transcutaneous auricular vagus nerve stimulation for post- ... ta-VNS has been proven effective as adjunctive therapy in patient with post-stroke depression. •. The synergistic approach of combining ta-VNS ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7416299/

Effect and Safety of Transcutaneous Auricular Vagus Nerve ... This study revealed that taVNS appeared to be beneficial to the recovery of upper limb motor function in subacute ischemia stroke patients without obvious ...

7. nature.com nature.com/articles/s41598-022-25864-1

Safety of transcutaneous auricular vagus nerve stimulation ... Although the general impression is that taVNS is a safe technique with only mild and transient adverse effects (AEs), human data on safety and ...