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

NCT03592745 | Completed Phase 2 Results FDA Device

• 1 other identifier: 18-0404
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke; Cerebrovascular Accident (CVA); Hemiparesis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (1)

• Median Change From Baseline in Upper Extremity Fugl Meyer Assessment Score

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

Study Arms (2)

active tVNS + robotic arm therapy

EXPERIMENTAL

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.

Device: Transcutaneous Vagus Nerve Stimulation (tVNS)

sham tVNS + robotic arm therapy

SHAM COMPARATOR

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.

Device: Sham Transcutaneous Vagus Nerve Stimulation (tVNS)

Interventions

Transcutaneous Vagus Nerve Stimulation (tVNS) DEVICE

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.

Also known as: Transauricular Vagus Nerve Stimulation

active tVNS + robotic arm therapy

Sham Transcutaneous Vagus Nerve Stimulation (tVNS) DEVICE

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.

Also known as: Sham Transauricular Vagus Nerve Stimulation

sham tVNS + robotic arm therapy

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Feinstein Institute for Medical Research

Manhasset, New York, 11030, United States

Location

Related Publications (7)

• 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.

  PMID: 26645257 BACKGROUND

• 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.

  PMID: 29375915 BACKGROUND

• 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.

  PMID: 24553102 BACKGROUND

• 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.

  PMID: 23954448 BACKGROUND

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

  PMID: 26671658 BACKGROUND

• 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.

  PMID: 19752297 BACKGROUND

• 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.

  PMID: 34899170 DERIVED

MeSH Terms

Conditions

Stroke; Paresis

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Research Coordinator
• Organization: Feinstein Institutes for Medical Research at Northwell Health

jchang14@northwell.edu

5165623646

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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).

Study Record Dates

• First Submitted: July 5, 2018
• First Posted: July 19, 2018
• Study Start: August 9, 2018
• Primary Completion: June 12, 2020
• Study Completion: June 1, 2021
• Last Updated: June 29, 2021
• Results First Posted: June 29, 2021

Record last verified: 2021-05

Locations

US (1)