Combining Non-Invasive Vagus Nerve Stimulation and Robotic Training in Upper Limb-Impaired Chronic Stroke Patients

Previous studies suggested that both robot-assisted rehabilitation and non-invasive vagus nerve stimulation can improve upper limb function in chronic stroke patients. Aim of present study is to explore whether the combination of these two approaches might enhance their positive effects on motor recovery. Safety and efficacy of this combination will be assessed within a proof-of-principle, double-blinded, randomized, sham-controlled trial. Transcutaneous vagus nerve stimulation (tVNS) will be delivered at left ear, in order to improve the response to the following robot-assisted therapy. Patients with both ischemic and hemorrhagic chronic stroke will be randomized to robot-assisted therapy associated with real or sham tVNS, delivered for 10 working days. Change in Fugl-Meyer has been chosen as primary outcome, while changes in several quantitative indicators of motor performance extracted by the robot as secondary outcomes.

Study Overview

• Status: Unknown
• Conditions: Stroke
• Intervention / Treatment: Device: Transcutaneous vagal nerve stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00128
    • Recruiting
    • Institute of Neurology, Campus Biomedico University
    • Contact: Vincenzo Di Lazzaro, MD; Phone Number: +39 06 22541 1320; Email: v.dilazzaro@unicampus.it
    • Principal Investigator: Fioravante Capone, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• first-ever ischemic or hemorrhagic stroke at least 1 year earlier
• hand function impairment
• ability to give informed consent and comprehend instructions

Exclusion Criteria:

• previous surgical intervention on vagus nerve
• low hearth rate (< 60 bpm)
• cognitive impairment or any substantial decrease in alertness, language reception, or attention that might interfere with understanding instructions for motor testing
• apraxia
• excessive pain in any joint of the paretic extremity
• advanced liver, kidney, cardiac or pulmonary disease
• history of significant alcohol or drug abuse
• depression or use of neuropsychotropic drugs such as antidepressants or benzodiazepines
• pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Robotic therapy and real tVNS; This group receives REAL vagus nerve stimulation during robotic rehabilitation.	Device: Transcutaneous vagal nerve stimulation; The stimulation of the auricular branch of the vagus nerve will be performed through an electric stimulator and two Ag-AgCl electrodes placed in the left external acoustic meatus at the inner side of the tragus. For sham stimulation, electrodes will be attached to the left ear lobe. tVNS will be delivered as trains lasting 30 s and composed by 600 pulses (intra-train pulse frequency = 20 Hz; pulse duration = 0.3 ms) repeated every 5 min for 60 min. The intensity of stimulation will individually adjusted to a level ranging above the detection threshold and below the pain threshold. In this range, when possible, the investigators will chose an intensity of 8 mA. Each day, for 10 consecutive working days, each patient will receive a session of robotic therapy during the real or sham tVNS stimulation
Active Comparator: Robotic therapy and sham tVNS; This group receives SHAM VNS during robotic rehabilitation. Sham VNS is not effective. Both groups receive the same amount of robotic rehabilitation.	Device: Transcutaneous vagal nerve stimulation; The stimulation of the auricular branch of the vagus nerve will be performed through an electric stimulator and two Ag-AgCl electrodes placed in the left external acoustic meatus at the inner side of the tragus. For sham stimulation, electrodes will be attached to the left ear lobe. tVNS will be delivered as trains lasting 30 s and composed by 600 pulses (intra-train pulse frequency = 20 Hz; pulse duration = 0.3 ms) repeated every 5 min for 60 min. The intensity of stimulation will individually adjusted to a level ranging above the detection threshold and below the pain threshold. In this range, when possible, the investigators will chose an intensity of 8 mA. Each day, for 10 consecutive working days, each patient will receive a session of robotic therapy during the real or sham tVNS stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Fugl-Meyer Score	immediately, one months and three months after the intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in kinematic data (Motion Accuracy) measured by the robot	immediately, one months and three months after the intervention
Change in kinematic data (Motion Direction) measured by the robot	immediately, one months and three months after the intervention
Change in kinematic data (Smoothness) measured by the robot	immediately, one months and three months after the intervention
Change in kinematic data (Speed) measured by the robot	immediately, one months and three months after the intervention
Change in kinematic data (Movement Duration) measured by the robot	immediately, one months and three months after the intervention
Change in kinematic data (Efficiency) measured by the robot	immediately, one months and three months after the intervention
Incidence of adverse events that are related to treatment	intervention period of 10 consecutive working days

Collaborators and Investigators

• Sponsor: Campus Bio-Medico University
• Collaborators: Biomedical Robotics and Biomicrosystems, Campus Bio-Medico University; Physical and Rehabilitation Medicine, Campus Bio-Medico University

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 24, 2016
• First Posted (Estimate): August 25, 2016

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 23, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: ischemic stroke; hemorrhagic chronic; non-invasive vagus nerve stimulation; robot-assisted rehabilitation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: VagusStroke

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No