tVNS Responsiveness Testing With Pupil Size

Movement-Associated tVNS and Responsiveness Testing for Personalized Rehabilitation

The goal of this study is to learn about the acute pupil response to transcutaneous vagus nerve stimulation (tVNS) in stroke survivors and healthy adults. The main question it aims to answer is whether pupil size response is greater with bilateral tVNS compared to unilateral tVNS. Participants will receive tVNS and sham at the outer ear unilaterally and bilaterally in resting condition. The pupil size of the participants will be recorded during tVNS.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Procedure: Bilateral tVNS stimulation; Procedure: Bilateral Sham stimulation; Procedure: Unilateral Left tVNS stimulation; Procedure: Unilateral Left Sham stimulation; Procedure: Unilateral Right tVNS stimulation; Procedure: Unilateral Right Sham stimulation

Detailed Description

Participants will wear surface electrodes on the outer ear on both sides and a finger device that monitors heart rate. The attachment sites are the tragus or the cymba concha (depending on the shape and size of the ear) for tVNS and the ear lobe for sham. The electrical current will have a pulse duration of 0.1 ms at 30 Hz with an intensity below the pain threshold or 5 milliamp, whichever is lower, for a duration of 0.5 s. The experimental stimulation intensity will be determined as just below the pain threshold. Participants will receive multiple blocks of unilateral and bilateral stimulations to the sham or tVNS electrodes at rest, during which their pupil size will be recorded. The order of unilateral/bilateral and sham/tVNS stimulation will be randomized.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Human Neuromuscular Physiology Lab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18-89 years old across all races, genders, and ethnicities.
• Post-stroke subjects will have persistent hemiparesis on the upper extremity (UE) with some residual UE voluntary movement.

Exclusion Criteria:

Able-bodied subjects:

• Younger than 18 years old or older than 89 years old
• Current or history of cardiac disease
• Have a vision problem not corrected by glasses or contact lenses
• Have an implanted device such as a neurostimulator or cochlear implant
• Current or history of tympanic membrane perforation
• Had a stroke or lesion (including tumor) in your brain
• Had a head injury or brain surgery
• Suffer from frequent or severe headaches
• Had a fainting spell or syncope
• Have any metal in the head such as shrapnel, surgical clips, or fragments from welding or metal work
• Have any implanted device such as cardiac pacemakers, medical pumps, or intra-cardiac lines
• Had any brain-related conditions (i.e. multiple sclerosis, Parkinson, Alzheimer)
• Had any illness that caused brain injury (i.e. meningitis, aneurysm, brain tumor)
• Had any head trauma that was associated with a loss of consciousness or diagnosed as a concussion
• Being treated for any psychiatric condition (i.e. depression, anxiety, PTSD, schizophrenia)
• Suspected of pregnancy

Post-stroke subjects:

• Younger than 18 years old or older than 89 years old
• Current or history of cardiac disease
• Have a vision problem not corrected by glasses or contact lenses
• Have any implanted devices such as a neurostimulator or cochlear implant
• Current or history of tympanic membrane perforation
• No persistent hemiparesis on the upper extremity (UE)
• No residual UE voluntary movement
• A first stroke less than 4 months prior to the participation
• Serious uncontrolled medical conditions
• Excessive pain in any joint of the more affected extremity
• Unable to stand independently for 2 min., transfer independently to and from the toilet or perform sit-to-stand
• Suffer from frequent or severe headaches
• Had a fainting spell or syncope
• Have any metal in the head such as shrapnel, surgical clips, or fragments from welding or metal work
• Have any implanted device such as cardiac pacemakers, medical pumps, or intra-cardiac lines
• Had any illness that caused brain injury (i.e. meningitis, aneurysm, brain tumor)
• Had any head trauma that was associated with a loss of consciousness or diagnosed as a concussion
• Being treated for any psychiatric condition (i.e. depression, anxiety, PTSD, schizophrenia)
• Suspected of pregnancy
• A score of less than 24 on the Folstein Mini-Mental State Examination
• Excessive frailty or lack of stamina (e.g., cannot attend to instructions, stay awake, engage in functional activities, etc.)
• Excessive pain in any joint of the more affected extremity that could limit ability to cooperate with the intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bilateral tVNS; Electrical stimulation to the vagus nerve area of the outer ear on both sides.	Procedure: Bilateral tVNS stimulation; Electrical stimulation to the cymba concha or tragus (depending on the ear dimension) of the outer ear on both sides after successful trials.
Sham Comparator: Bilateral Sham; Electrical stimulation to the non-vagus nerve area of the outer ear on both sides.	Procedure: Bilateral Sham stimulation; Electrical stimulation to the earlobe of the outer ear on both sides after successful trials.
Experimental: Unilateral Left tVNS; Electrical stimulation to the vagus nerve area of the outer ear on the left side.	Procedure: Unilateral Left tVNS stimulation; Electrical stimulation to the cymba concha or tragus (depending on the ear dimension) of the outer ear on the left side after successful trials.
Sham Comparator: Unilateral Left Sham; Electrical stimulation to the non-vagus nerve area of the outer ear on the left side.	Procedure: Unilateral Left Sham stimulation; Electrical stimulation to the earlobe of the outer ear on the left side after successful trials.
Experimental: Unilateral Right tVNS; Electrical stimulation to the vagus nerve area of the outer ear on the right side.	Procedure: Unilateral Right tVNS stimulation; Electrical stimulation to the cymba concha or tragus (depending on the ear dimension) of the outer ear on the right side after successful trials.
Sham Comparator: Unilateral Right Sham; Electrical stimulation to the non-vagus nerve area of the outer ear on the right side.	Procedure: Unilateral Right Sham stimulation; Electrical stimulation to the earlobe of the outer ear on the right side after successful trials.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pupil size change	Acute change in pupil size in response to electrical stimulation, relatively expressed as a percent change from the baseline	Day 1

Collaborators and Investigators

• Sponsor: Georgia Institute of Technology
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Emory University
• Investigators: Principal Investigator: Minoru Shinohara, Ph.D., Georgia Institute of Technology

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2024
• Primary Completion (Actual): October 27, 2025
• Study Completion (Actual): October 27, 2025

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Estimated): October 29, 2025
• Last Update Submitted That Met QC Criteria: October 28, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: H24109; 5P2CHD086844-09 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data on pupil size change will be available to other researchers outside the primary research group.
• IPD Sharing Time Frame: The data will become available after the publication of all papers from the study.
• IPD Sharing Access Criteria: The scientific data will be made available by a data repository after approval.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No