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Transcutaneous Vagus Nerve Stimulation (tVNS) and Robotic Training to Improve Arm Function After Stroke (tVNS)

Primary Purpose

Stroke, Cerebrovascular Accident (CVA), Hemiparesis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Transcutaneous Vagus Nerve Stimulation (tVNS)

Sham Transcutaneous Vagus Nerve Stimulation (tVNS)

About this trial

This is an interventional treatment trial for Stroke focused on measuring Transcutaneous vagus nerve stimulation (tVNS), VNS, robotic therapy, occupational therapy, motor rehabilitation

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Individuals between 18 and 85 years of age
First single focal unilateral supratentorial ischemic stroke with diagnosis verified by brain imaging (MRI or CT scans) that occurred at least 6 months prior
Cognitive function sufficient to understand the experiments and follow instructions (per interview with Speech Pathologist or PI)
Fugl-Meyer assessment 12 to 44 out of 66 (neither hemiplegic nor fully recovered motor function in the muscles of the shoulder, elbow, and wrist).

Exclusion Criteria:

Botox treatment within 3 months of enrollment
Fixed contraction deformity in the affected limb
Complete and total flaccid paralysis of all shoulder and elbow motor performance
Prior injury to the vagus nerve
Severe dysphagia
Introduction of any new rehabilitation interventions during study
Individuals with scar tissue, broken skin, or irremovable metal piercings that may interfere with the stimulation or the stimulation device
Highly conductive metal in any part of the body, including metal injury to the eye; this will be reviewed on a case by case basis for PI to make a determination
Pregnant or plan on becoming pregnant or breastfeeding during the study period
Significant arrhythmias, including but not limited to, atrial fibrillation, atrial flutter, sick sinus syndrome, and A-V blocks (enrollment to be determined by PI review)
Presence of an electrically, magnetically or mechanically activated implant (including cardiac pacemaker), an intracerebral vascular clip, or any other electrically sensitive support system; Loop recorders will be reviewed on a case by case basis by PI and the treating Cardiologist to make a determination

Sites / Locations

Feinstein Institute for Medical Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

active tVNS + robotic arm therapy

sham tVNS + robotic arm therapy

Arm Description

Transcutaneous Vagus Nerve Stimulation (tVNS) will be delivered non-invasively via the ear (targeting the auricular branch of the vagus nerve) during robotic arm therapy sessions lasting ~60 minutes, 3x per week for 3 weeks.

Sham (placebo) transcutaneous Vagus Nerve Stimulation (tVNS) will be delivered non-invasively via the ear (targeting the auricular branch of the vagus nerve) during robotic arm therapy sessions lasting ~60 minutes, 3x per week for 3 weeks.

Outcomes

Primary Outcome Measures

Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep

The median absolute change in surface electromyographic (sEMG) peak amplitude of the bicep/tricep during gravity-eliminated, unassisted extensor movements was calculated from baseline to discharge at 3 weeks (immediately following the intervention) and again at 16 weeks (3 months follow-up from the intervention) in each training condition (sham tVNS + robotic arm training vs. active tVNS + robotic arm training). Bicep and tricep peak sEMG amplitude scores were calculated as a percentage of the maximal volitional contraction (MVC), with larger values indicating a greater absolute change (negative or positive) in bicep/tricep peak muscle activity during extensor movements.

Secondary Outcome Measures

Median Change From Baseline in Upper Extremity Fugl Meyer Assessment Score

The median change in Upper Extremity Fugl-Meyer Score will be calculated from baseline to discharge at 3 weeks (immediately following the intervention) and again at 16 weeks (3 months follow-up from the intervention) in each training condition (sham tVNS + robotic arm training vs. active tVNS + robotic arm training). The median change in Upper Extremity Fugl Meyer score is reported, with a range 0-66 points, and with higher values indicating better functional status.

Full Information

NCT ID

NCT03592745

First Posted

July 5, 2018

Last Updated

June 8, 2021

Sponsor

Northwell Health

1. Study Identification

Unique Protocol Identification Number

NCT03592745

Brief Title

Transcutaneous Vagus Nerve Stimulation (tVNS) and Robotic Training to Improve Arm Function After Stroke

Acronym

tVNS

Official Title

Evaluating the Use of Transcutaneous Vagus Nerve Stimulation (tVNS) and Robotic Training to Improve Upper Limb Motor Recovery After Stroke

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

August 9, 2018 (Actual)

Primary Completion Date

June 12, 2020 (Actual)

Study Completion Date

June 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwell Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate if multiple therapy sessions of Transcutaneous Vagus Nerve Stimulation (tVNS) combined with robotic arm therapy lead to a greater functional recovery in upper limb mobility after stroke than that provided by robotic arm therapy in a sham stimulation condition.

Detailed Description

Promising new animal research suggests that vagus nerve stimulation paired with motor intervention induces movement-specific plasticity in the motor cortex and improves limb function after stroke. These results were recently extended to the first clinical trial, in which patients with stroke demonstrated significant improvements in upper limb function following rehabilitation paired with implanted VNS. Currently, vagus nerve stimulation is being used clinically to treat a number of human diseases including migraine headaches, epilepsy, and depression, and these investigations are expanding to deliver stimulation via a transcutaneous route to potentially improve intervention efficacy and decrease side effects. This pilot study will combine non-invasive transcutaneous stimulation of the vagus nerve with upper limb robotic therapy to investigate the potential of tVNS to augment improvements gained with robotic therapy in patients with chronic hemiparesis after stroke.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stroke, Cerebrovascular Accident (CVA), Hemiparesis

Keywords

Transcutaneous vagus nerve stimulation (tVNS), VNS, robotic therapy, occupational therapy, motor rehabilitation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

This is a double-blind, sham controlled treatment study in which patients will have a 50/50 chance of receiving robotic arm therapy with either active transcutaneous vagus nerve stimulation (tVNS) or sham tVNS (placebo).

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Both the participants and investigators performing and analyzing clinical and objective outcome measures will remain blind to condition. Participants will be told that they have a 50-50 chance of receiving either active or sham stimulation, but they will not be told which condition they receive.

Allocation

Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

active tVNS + robotic arm therapy

Arm Type

Experimental

Arm Description

Arm Title

sham tVNS + robotic arm therapy

Arm Type

Sham Comparator

Arm Description

Intervention Type

Device

Intervention Name(s)

Transcutaneous Vagus Nerve Stimulation (tVNS)

Other Intervention Name(s)

Transauricular Vagus Nerve Stimulation

Intervention Description

tVNS is a non-invasive form of vagus nerve stimulation, activating the auricular branch of the vagus nerve transcutaneously through the cymba concha at the pinna of the ear.

Intervention Type

Device

Intervention Name(s)

Sham Transcutaneous Vagus Nerve Stimulation (tVNS)

Other Intervention Name(s)

Sham Transauricular Vagus Nerve Stimulation

Intervention Description

tVNS is a non-invasive form of vagus nerve stimulation, activating the auricular branch of the vagus nerve transcutaneously through the cymba concha at the pinna of the ear. Sham tVNS means the patient is wearing the device, but it is turned off and not delivering current during the treatment. This is a placebo condition, which is used as a study control.

Primary Outcome Measure Information:

Title

Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep

Description

Time Frame

baseline, discharge at 3 weeks (immediately following the intervention), and follow-up at 16 weeks (3 months after the intervention)

Secondary Outcome Measure Information:

Title

Median Change From Baseline in Upper Extremity Fugl Meyer Assessment Score

Description

Time Frame

baseline, discharge at 3 weeks (immediately following the intervention), and follow-up at 16 weeks (3 months after the intervention)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Individuals between 18 and 85 years of age First single focal unilateral supratentorial ischemic stroke with diagnosis verified by brain imaging (MRI or CT scans) that occurred at least 6 months prior Cognitive function sufficient to understand the experiments and follow instructions (per interview with Speech Pathologist or PI) Fugl-Meyer assessment 12 to 44 out of 66 (neither hemiplegic nor fully recovered motor function in the muscles of the shoulder, elbow, and wrist). Exclusion Criteria: Botox treatment within 3 months of enrollment Fixed contraction deformity in the affected limb Complete and total flaccid paralysis of all shoulder and elbow motor performance Prior injury to the vagus nerve Severe dysphagia Introduction of any new rehabilitation interventions during study Individuals with scar tissue, broken skin, or irremovable metal piercings that may interfere with the stimulation or the stimulation device Highly conductive metal in any part of the body, including metal injury to the eye; this will be reviewed on a case by case basis for PI to make a determination Pregnant or plan on becoming pregnant or breastfeeding during the study period Significant arrhythmias, including but not limited to, atrial fibrillation, atrial flutter, sick sinus syndrome, and A-V blocks (enrollment to be determined by PI review) Presence of an electrically, magnetically or mechanically activated implant (including cardiac pacemaker), an intracerebral vascular clip, or any other electrically sensitive support system; Loop recorders will be reviewed on a case by case basis by PI and the treating Cardiologist to make a determination

Facility Information:

Facility Name

Feinstein Institute for Medical Research

City

Manhasset

State/Province

New York

ZIP/Postal Code

11030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

26645257

Citation

Dawson J, Pierce D, Dixit A, Kimberley TJ, Robertson M, Tarver B, Hilmi O, McLean J, Forbes K, Kilgard MP, Rennaker RL, Cramer SC, Walters M, Engineer N. Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke. Stroke. 2016 Jan;47(1):143-50. doi: 10.1161/STROKEAHA.115.010477. Epub 2015 Dec 8.

Results Reference

background

PubMed Identifier

29375915

Citation

Capone F, Miccinilli S, Pellegrino G, Zollo L, Simonetti D, Bressi F, Florio L, Ranieri F, Falato E, Di Santo A, Pepe A, Guglielmelli E, Sterzi S, Di Lazzaro V. Transcutaneous Vagus Nerve Stimulation Combined with Robotic Rehabilitation Improves Upper Limb Function after Stroke. Neural Plast. 2017;2017:7876507. doi: 10.1155/2017/7876507. Epub 2017 Dec 10.

Results Reference

background

PubMed Identifier

24553102

Citation

Khodaparast N, Hays SA, Sloan AM, Fayyaz T, Hulsey DR, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke. Neurorehabil Neural Repair. 2014 Sep;28(7):698-706. doi: 10.1177/1545968314521006. Epub 2014 Feb 18.

Results Reference

background

PubMed Identifier

23954448

Citation

Khodaparast N, Hays SA, Sloan AM, Hulsey DR, Ruiz A, Pantoja M, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke. Neurobiol Dis. 2013 Dec;60:80-8. doi: 10.1016/j.nbd.2013.08.002. Epub 2013 Aug 15.

Results Reference

background

PubMed Identifier

26671658

Citation

Hays SA. Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation. Neurotherapeutics. 2016 Apr;13(2):382-94. doi: 10.1007/s13311-015-0417-z.

Results Reference

background

PubMed Identifier

19752297

Citation

Volpe BT, Huerta PT, Zipse JL, Rykman A, Edwards D, Dipietro L, Hogan N, Krebs HI. Robotic devices as therapeutic and diagnostic tools for stroke recovery. Arch Neurol. 2009 Sep;66(9):1086-90. doi: 10.1001/archneurol.2009.182.

Results Reference

background

PubMed Identifier

34899170

Citation

Chang JL, Coggins AN, Saul M, Paget-Blanc A, Straka M, Wright J, Datta-Chaudhuri T, Zanos S, Volpe BT. Transcutaneous Auricular Vagus Nerve Stimulation (tAVNS) Delivered During Upper Limb Interactive Robotic Training Demonstrates Novel Antagonist Control for Reaching Movements Following Stroke. Front Neurosci. 2021 Nov 25;15:767302. doi: 10.3389/fnins.2021.767302. eCollection 2021.

Results Reference

derived

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Transcutaneous Vagus Nerve Stimulation (tVNS) and Robotic Training to Improve Arm Function After Stroke

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