Pupil-Indexed Noninvasive Neuromodulation

NCT ID: NCT06282406

Last Updated: 2025-06-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-03

Study Completion Date

2028-08-05

Brief Summary

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Vagus nerve stimulation (VNS) is thought to activate neural pathways that release chemicals which promote plasticity and learning. Previous work has shown that the auricular branch of the vagus nerve innervates landmarks on the external ear. Work from the PI's laboratory has shown that electrical current applied to the external ear modulates physiological indexes of brain states implicated in the therapeutic effects of VNS. The broad objective of this project is to better understand physiological mechanisms modulated by auricular stimulation to support possible therapeutic effects in the form of motor learning.

Detailed Description

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Existing evidence supports the use of VNS to enhance the effects of traditional therapy on impairments due to neurological injury. It is known that the vagus nerve forms contacts with neuromodulatory nuclei in the brainstem that release of chemicals shown to be critically involved in attentional control and memory formation. It is also known that the auricular branch of the vagus nerve innervates portions of the external ear providing a possible means to engage similar neural pathways noninvasively via transcutaneous auricular vagus nerve stimulation (taVNS). Recent work from the PI's laboratory shows that electrical current applied to landmarks on the external ear elicits transient effects on pupil dilation, an established physiological index of brain states that support learning. Given the ability to engage the biomarker, the investigators aim to further investigate physiological mechanisms modulated by taVNS and possible effects on learning.

Conditions

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Paresis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Subjects will be randomized into one of 5 groups and receive the designated stimulation/sham during a training protocol designed to facilitate motor learning.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Paired, Sub-Threshold Stim

Sub-threshold stimulation paired with successful task repetitions

Group Type EXPERIMENTAL

Transcutaneous Electrical Stimulation

Intervention Type OTHER

Electrical pulse trains applied to the skin overlying putative sites of auricular vagal innervation.

Paired, Supra-Threshold Stim

Supra-threshold stimulation paired with successful task repetition

Group Type EXPERIMENTAL

Transcutaneous Electrical Stimulation

Intervention Type OTHER

Electrical pulse trains applied to the skin overlying putative sites of auricular vagal innervation.

Unpaired, Sub-Threshold Stim

Sub-threshold stimulation after successful task repetition

Group Type EXPERIMENTAL

Transcutaneous Electrical Stimulation

Intervention Type OTHER

Electrical pulse trains applied to the skin overlying putative sites of auricular vagal innervation.

Unpaired, Supra-Threshold Stim

Supra-threshold stimulation after successful task repetition

Group Type EXPERIMENTAL

Transcutaneous Electrical Stimulation

Intervention Type OTHER

Electrical pulse trains applied to the skin overlying putative sites of auricular vagal innervation.

Sham

No stimulation

Group Type SHAM_COMPARATOR

Sham

Intervention Type OTHER

Electrodes placed on the skin overlying putative sites of auricular vagal innervation but no current administered.

Interventions

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Transcutaneous Electrical Stimulation

Electrical pulse trains applied to the skin overlying putative sites of auricular vagal innervation.

Intervention Type OTHER

Sham

Electrodes placed on the skin overlying putative sites of auricular vagal innervation but no current administered.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

ALL PROSPECTIVE SUBJECTS:

1. 18-75 years of age

PROSPECTIVE SUBJECTS DIAGNOSED WITH STROKE:
2. Diagnosis of a single stroke resulting in hand impairment
3. Diagnosis of stroke at least six months prior to the time of participation

Exclusion Criteria

ALL PROSPECTIVE SUBJECTS:

1. History of vestibular disorders or dizziness
2. Difficulty maintaining alertness and/or remaining still
3. Pregnant or expecting to become pregnant
4. Diagnosis of neurological and/or musculoskeletal disorder(s) (other than stroke) that affect movement
5. Ocular disease and/or impairment in more than one eye
6. History of seizure and/or epilepsy
7. Implants, devices, or foreign objects in the brain/body that are incompatible with MRI
8. Body size that is incompatible with MRI scanner dimensions
9. Anyone already enrolled and actively participating in another greater than minimal risk study.

PROSPECTIVE SUBJECTS DIAGNOSED WITH STROKE:
10. Other impairments secondary to stroke (e.g., attention, cognition, etc.) that would interfere with the ability to understand study goals or follow simple instructions, as judged by the investigators.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael A. Urbin, PhD

Role: PRINCIPAL_INVESTIGATOR

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Locations

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VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Michael A Urbin, PhD

Role: CONTACT

(412) 688-6000

Brad E Dicianno, MD MS

Role: CONTACT

(412) 822-3700

Facility Contacts

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Elizabeth B Toth, BA

Role: primary

412-954-5382

Kimberly A Toland

Role: backup

(412) 215-5084

References

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Dawson J, Liu CY, Francisco GE, Cramer SC, Wolf SL, Dixit A, Alexander J, Ali R, Brown BL, Feng W, DeMark L, Hochberg LR, Kautz SA, Majid A, O'Dell MW, Pierce D, Prudente CN, Redgrave J, Turner DL, Engineer ND, Kimberley TJ. Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial. Lancet. 2021 Apr 24;397(10284):1545-1553. doi: 10.1016/S0140-6736(21)00475-X.

Reference Type BACKGROUND
PMID: 33894832 (View on PubMed)

Follesa P, Biggio F, Gorini G, Caria S, Talani G, Dazzi L, Puligheddu M, Marrosu F, Biggio G. Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain. Brain Res. 2007 Nov 7;1179:28-34. doi: 10.1016/j.brainres.2007.08.045. Epub 2007 Aug 25.

Reference Type BACKGROUND
PMID: 17920573 (View on PubMed)

Roosevelt RW, Smith DC, Clough RW, Jensen RA, Browning RA. Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat. Brain Res. 2006 Nov 13;1119(1):124-32. doi: 10.1016/j.brainres.2006.08.048. Epub 2006 Sep 7.

Reference Type BACKGROUND
PMID: 16962076 (View on PubMed)

Safi S, Ellrich J, Neuhuber W. Myelinated Axons in the Auricular Branch of the Human Vagus Nerve. Anat Rec (Hoboken). 2016 Sep;299(9):1184-91. doi: 10.1002/ar.23391. Epub 2016 Jul 12.

Reference Type BACKGROUND
PMID: 27342906 (View on PubMed)

Butt MF, Albusoda A, Farmer AD, Aziz Q. The anatomical basis for transcutaneous auricular vagus nerve stimulation. J Anat. 2020 Apr;236(4):588-611. doi: 10.1111/joa.13122. Epub 2019 Nov 19.

Reference Type BACKGROUND
PMID: 31742681 (View on PubMed)

Urbin MA, Lafe CW, Simpson TW, Wittenberg GF, Chandrasekaran B, Weber DJ. Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans. Brain Stimul. 2021 Jul-Aug;14(4):990-1001. doi: 10.1016/j.brs.2021.06.002. Epub 2021 Jun 18.

Reference Type BACKGROUND
PMID: 34154980 (View on PubMed)

Other Identifiers

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I0X1RX004532

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

N4532-R

Identifier Type: -

Identifier Source: org_study_id

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