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

Stroke Clinical Trial

— tVNS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03592745
• Other study ID #: 18-0404
• Status: Completed
• Phase: Phase 2
• Start date: August 9, 2018
• Est. completion date: June 1, 2021

Study information

• Verified date: May 2021
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 1, 2021
• Est. primary completion date: June 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebrovascular Accident (CVA)
• Hemiparesis
• Paresis
• Stroke

Intervention

Device:
• Transcutaneous Vagus Nerve Stimulation (tVNS)
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 Transcutaneous Vagus Nerve Stimulation (tVNS)
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.

Locations

Country	Name	City	State
United States	Feinstein Institute for Medical Research	Manhasset	New York

Sponsors (1)

Lead Sponsor	Collaborator
Northwell Health

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View 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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	baseline, discharge at 3 weeks (immediately following the intervention), and follow-up at 16 weeks (3 months after the intervention)