taVNS + Robotic Arm Training for Stroke

(VaNSaRTS Trial)

Overseen By Celina B Fernandez, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwell Health

Disqualifiers: Pregnancy, Arrhythmias, Vagus nerve injury, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

45 Participants Needed

Trial Summary

What is the purpose of this trial?

To determine whether treatment with transauricular vagus nerve stimulation (taVNS) during the training of an affected upper limb of a patient with chronic stroke on a robotic motor task alters the motor impairment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that you cannot introduce any new rehabilitation interventions during the study.

What data supports the effectiveness of the treatment taVNS + Robotic Arm Training for Stroke?

Research shows that robotic arm training, like the MIT-MANUS and H-Man, helps improve motor control in stroke patients, especially for shoulder and elbow movements. Studies indicate that robot-aided therapy can be as effective as conventional therapy, suggesting that combining it with taVNS might enhance recovery. ^{1 2 3 4 5}

Is the combination of taVNS and robotic arm training safe for stroke rehabilitation?

The ArmAssist robotic device, used for arm training in stroke patients, was found to be safe with no adverse events reported in a study. This suggests that robotic arm training is generally safe for stroke rehabilitation. ^{2 6 7 8 9}

How is the taVNS + Robotic Arm Training treatment different from other stroke treatments?

This treatment combines transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive method, with robotic arm training to improve arm function after a stroke. Unlike traditional therapies, it specifically targets the premotor planning stage to enhance motor control and reduce spasticity, offering a novel approach to stroke rehabilitation. ^{2 10 11 12 13}

Research Team

Bruce T Volpe, MD

Principal Investigator

Feinstein Center for Molecular Medicine

Timir Datta Chaudhuri, PhD

Principal Investigator

Feinstein Center for Bioelectronic Medicine

Eligibility Criteria

This trial is for adults aged 18-85 who've had a single stroke at least 6 months ago, with some arm movement but not fully recovered. They must be vaccinated, have no recent respiratory issues or taste/smell loss, and can't be pregnant or breastfeeding. People with vagus nerve damage, severe swallowing difficulties, certain implants, metal injuries to the eye or arrhythmias are excluded.

Inclusion Criteria

I am fully vaccinated and have not had recent cold symptoms or lost my sense of taste or smell.

My arm movement is limited but not completely lost.

I had a stroke in the upper part of my brain at least 6 months ago, confirmed by MRI or CT.

Exclusion Criteria

You have an implanted device that can be affected by electricity, magnetism, or mechanical forces, such as a pacemaker. Any decision about participants with loop recorders will be made by the principal investigator and the treating cardiologist on a case-by-case basis.

You have metal in your body, such as a metal implant or a metal injury in the eye. Each case will be reviewed individually by the principal investigator to decide if you can participate.

I cannot move my shoulders or elbows at all.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Unaffected Limb Training

Participants engage the robot with their unaffected limb to ensure understanding and activate the hemisphere ipsilateral to the impaired limb. No taVNS is applied during this phase.

1 session

1 visit (in-person)

Affected Limb Training with taVNS

Participants wear the taVNS device on the left ear and engage the robotic device with the affected limb. Stimulation or sham stimulation occurs with every extensor movement.

4-6 weeks

Multiple sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• In Motion Rehabilitation Robot
• Trans Auricular Vagus Nerve Stimulation (taVNS)

Trial Overview The study tests if taVNS (a non-invasive ear stimulation) combined with robotic training helps improve arm function in chronic stroke patients. Participants will use an In Motion Rehabilitation Robot while receiving taVNS to see if it enhances motor recovery compared to robot training alone.

Participant Groups

Group I: Unaffected limb Active Control 1 Intervention

Patients will engage the robot first with their unaffected limb. This practice will ensure understanding and serve to activate the hemisphere ipsilateral to the impaired limb. Patients are likely to perform this activity quickly, there will not be any taVNS during this part of the procedure.

Group II: Affected Limb Placebo Group 1 Intervention

Patients will wear the taVNS device on the left ear for the duration of the subsequent phase of the robotic training. During this phase the patient will engage the robotic device with the affected limb and complete the protocol and the stimulation or sham stimulation will occur with every extensor movement. Within subject. Sham controlled. Double blind, the patient will not know whether they are receiving taVNS, all patients feel a ramp up current but only the active group will receive timed stimulation bursts during the robotic protocol that engages the affected limb. '

In Motion Rehabilitation Robot is already approved in United States for the following indications:

Approved in United States as InMotion ARM for:

• Stroke
• Spinal Cord Injury
• Multiple Sclerosis
• Parkinson’s Disease
• Cerebral Palsy

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Findings from Research

The MIT-MANUS robot has been effective in rehabilitating shoulder and elbow movements in stroke patients, showing a reduction in movement impairment during clinical trials.

A new wrist rehabilitation robot is being tested in a clinical trial with 200 stroke survivors, and initial results from 36 participants suggest that training with this device may lead to further improvements in motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robot-aided neurorehabilitation: a robot for wrist rehabilitation. Krebs, HI., Volpe, BT., Williams, D., et al.[2018]

The EMG-driven neuromuscular electrical stimulation (NMES)-robot arm significantly improved upper limb function in subacute stroke patients, particularly in wrist and hand movements, compared to traditional therapy, as shown by higher scores in the Fugl-Meyer Assessment and Action Research Arm Test after 20 training sessions.

The NMES-robot group not only achieved better motor outcomes but also demonstrated a reduction in muscle tone, indicating improved muscular coordination, which was maintained for 3 months post-treatment, while the control group showed increased muscle tone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Stroke Rehabilitation of the Upper Limb Assisted with an Electromyography-Driven Neuromuscular Electrical Stimulation-Robotic Arm. Qian, Q., Hu, X., Lai, Q., et al.[2022]

A study involving 44 stroke survivors showed that a combination of robotic-aided therapy (RAT) and conventional therapy led to significant improvements in upper limb function, with the RAT group achieving similar clinical outcomes while reducing therapist time by two-thirds.

Both therapy groups demonstrated sustained improvements in motor function 18 weeks after training, with no adverse side effects reported, suggesting that RAT can be a safe and effective alternative to traditional rehabilitation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robotic Assisted Upper Limb Training Post Stroke: A Randomized Control Trial Using Combinatory Approach Toward Reducing Workforce Demands. Budhota, A., Chua, KSG., Hussain, A., et al.[2021]

In a study of 36 subacute stroke patients undergoing robotic training, responders showed a decrease in practice time and movements in assisted modalities, while non-responders increased their practice time and movements, indicating different engagement levels during therapy.

Despite non-responders practicing more, their motor outcomes did not improve, suggesting that the robotic training may not have been challenging enough for them, highlighting the need for tailored interventions based on individual capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance-Based Robotic Training in Individuals with Subacute Stroke: Differences between Responders and Non-Responders. Pila, O., Duret, C., Koeppel, T., et al.[2023]

Robot-aided therapy significantly improves motor control of the shoulder and elbow in stroke patients with hemiparesis, based on a review of eight clinical trials.

While robot-aided therapy shows better motor control outcomes compared to conventional therapy, it does not consistently enhance overall functional abilities in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of the effect of robot-aided therapy on recovery of the hemiparetic arm after stroke. Prange, GB., Jannink, MJ., Groothuis-Oudshoorn, CG., et al.[2022]

The ArmAssist robotic system significantly improved upper limb motor function in subacute stroke patients compared to conventional training, with a notable increase in Fugl-Meyer Assessment scores (18.0 vs. 7.5) after 3 weeks of training.

The study involved 26 participants who trained 5 days a week for 3 weeks, and importantly, there were no adverse events reported, indicating that the ArmAssist is a safe intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ArmAssist Robotic System versus Matched Conventional Therapy for Poststroke Upper Limb Rehabilitation: A Randomized Clinical Trial. Tomić, TJ., Savić, AM., Vidaković, AS., et al.[2018]

This study aims to investigate the impact of both the timing and dosing of robotic and virtual reality therapy on upper extremity recovery in stroke patients, with a focus on starting therapy either early (5-30 days post-stroke) or delayed (30-60 days post-stroke).

The primary outcome will be measured using the Action Research Arm Test (ARAT) at 4 months post-stroke, which will help determine the optimal timing for rehabilitation interventions to maximize recovery of arm function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hand Focused Upper Extremity Rehabilitation in the Subacute Phase Post-stroke Using Interactive Virtual Environments. Merians, AS., Fluet, GG., Qiu, Q., et al.[2020]

The Neurofenix platform for home-based upper limb rehabilitation is safe and well-accepted, with participants reporting lower odds of shoulder pain after 8 and 12 weeks of use compared to baseline.

Participants showed improvements in upper extremity function and activity levels, completing a median of 17.4 hours of training over 7 weeks, indicating the platform's feasibility for supporting rehabilitation post-stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, feasibility, acceptability and preliminary effects of the Neurofenix platform for Rehabilitation via HOMe Based gaming exercise for the Upper-limb post Stroke (RHOMBUS): results of a feasibility intervention study. Kilbride, C., Scott, DJM., Butcher, T., et al.[2022]

In a study involving 54 stroke patients, robot-assisted therapy using the Mirror Image Movement Enabler (MIME) did not show significant differences in primary motor function outcomes compared to conventional therapy at the 6-month follow-up.

However, higher intensity and dosage of MIME therapy were positively correlated with improvements in motor function, suggesting that more intensive training may enhance rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robot-assisted upper-limb therapy in acute rehabilitation setting following stroke: Department of Veterans Affairs multisite clinical trial. Burgar, CG., Lum, PS., Scremin, AM., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) combined with robotic training significantly reduced wrist and hand spasticity in chronic stroke patients, showing a notable improvement compared to the sham group.

Both active and sham taVNS groups experienced motor improvements, but the active taVNS group demonstrated enhanced muscle activation and control, particularly in the biceps, indicating that taVNS may optimize rehabilitation outcomes by improving muscle coordination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation (tAVNS) Delivered During Upper Limb Interactive Robotic Training Demonstrates Novel Antagonist Control for Reaching Movements Following Stroke. Chang, JL., Coggins, AN., Saul, M., et al.[2021]

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]

A systematic review of 38 randomized controlled trials involving 1261 participants found that transcutaneous vagus nerve stimulation (tVNS) and anodal transcranial direct current stimulation (tDCS) significantly improve upper limb motor function and activities of daily living (ADL) after stroke.

tVNS was ranked as the most effective treatment for enhancing motor function and ADL performance, with no significant safety concerns compared to control interventions, indicating its potential as a safe and effective rehabilitation strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Adjunct of Electric Neurostimulation to Rehabilitation Approaches in Upper Limb Stroke Rehabilitation: A Systematic Review With Network Meta-Analysis of Randomized Controlled Trials. Ahmed, I., Yeldan, I., Mustafaoglu, R.[2022]

The FDA has approved a paired vagus nerve stimulation (VNS) system that, when combined with rehabilitation therapy, significantly improves upper extremity function in patients with moderate-to-severe arm weakness after chronic ischemic stroke, as shown in a Phase III trial with an average follow-up of 3 years.

Patients receiving VNS therapy experienced a clinically meaningful improvement of at least six points on the Fugl-Meyer score, with about 50% achieving this response compared to only 25% in those receiving rehabilitation alone, indicating the potential effectiveness of VNS in enhancing recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paired vagus nerve stimulation for treatment of upper extremity impairment after stroke. Dawson, J., Abdul-Rahim, AH.[2022]

References

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

Robot-aided neurorehabilitation: a robot for wrist rehabilitation. [2018]

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

Early Stroke Rehabilitation of the Upper Limb Assisted with an Electromyography-Driven Neuromuscular Electrical Stimulation-Robotic Arm. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Robotic Assisted Upper Limb Training Post Stroke: A Randomized Control Trial Using Combinatory Approach Toward Reducing Workforce Demands. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Performance-Based Robotic Training in Individuals with Subacute Stroke: Differences between Responders and Non-Responders. [2023]

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

Systematic review of the effect of robot-aided therapy on recovery of the hemiparetic arm after stroke. [2022]

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

ArmAssist Robotic System versus Matched Conventional Therapy for Poststroke Upper Limb Rehabilitation: A Randomized Clinical Trial. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Hand Focused Upper Extremity Rehabilitation in the Subacute Phase Post-stroke Using Interactive Virtual Environments. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Safety, feasibility, acceptability and preliminary effects of the Neurofenix platform for Rehabilitation via HOMe Based gaming exercise for the Upper-limb post Stroke (RHOMBUS): results of a feasibility intervention study. [2022]

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

Robot-assisted upper-limb therapy in acute rehabilitation setting following stroke: Department of Veterans Affairs multisite clinical trial. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation (tAVNS) Delivered During Upper Limb Interactive Robotic Training Demonstrates Novel Antagonist Control for Reaching Movements Following Stroke. [2021]

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

Clinical Research Progress of the Post-Stroke Upper Limb Motor Function Improvement via Transcutaneous Auricular Vagus Nerve Stimulation. [2023]

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

The Adjunct of Electric Neurostimulation to Rehabilitation Approaches in Upper Limb Stroke Rehabilitation: A Systematic Review With Network Meta-Analysis of Randomized Controlled Trials. [2022]

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

Paired vagus nerve stimulation for treatment of upper extremity impairment after stroke. [2022]