VNS-induced Corticospinal Plasticity

NCT ID: NCT04088565

Last Updated: 2022-11-01

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

COMPLETED

Clinical Phase

NA

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-22

Study Completion Date

2021-11-09

Brief Summary

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The goal of this study is to learn more about the connections between the brain, spinal cord, and muscles and how these connections can be strengthened after neurological injury.

Detailed Description

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Non-invasive stimulation techniques can be used to appropriately time converging inputs to induce changes in cortical output circuits of human primary motor cortex, a neuromodulatory protocol known as paired-associative stimulation (PAS). Experiments seek to examine interactions between cortical PAS and non-invasive vagus nerve stimulation (VNS) to understand the extent to which VNS amplifies cortical plasticity in humans.

Conditions

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Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

SINGLE

Participants

Study Groups

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PAS+VNS

Paired-associative stimulation (PAS) targeting primary motor cortex will be administered with VNS in individuals with hemiparesis secondary to stroke and neurologically-intact, age-matched controls.

Group Type EXPERIMENTAL

Paired-Associative Stimulation (PAS)

Intervention Type OTHER

Simultaneous activation of connections in motor cortex via stimulation to the nerves and brain.

Vagus Nerve Stimulation (VNS)

Intervention Type OTHER

Recruits the auricular branch of the vagus nerve which activates brain structures that release chemicals mediating cortical plasticity.

PAS+Sham

Paired-associative stimulation (PAS) targeting primary motor cortex will be administered with sham stimulation in individuals with hemiparesis secondary to stroke and neurologically-intact, age-matched controls.

Group Type SHAM_COMPARATOR

Paired-Associative Stimulation (PAS)

Intervention Type OTHER

Simultaneous activation of connections in motor cortex via stimulation to the nerves and brain.

Sham Stimulation

Intervention Type OTHER

Sub-threshold stimulation that does not activate neural structures.

Interventions

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Paired-Associative Stimulation (PAS)

Simultaneous activation of connections in motor cortex via stimulation to the nerves and brain.

Intervention Type OTHER

Vagus Nerve Stimulation (VNS)

Recruits the auricular branch of the vagus nerve which activates brain structures that release chemicals mediating cortical plasticity.

Intervention Type OTHER

Sham Stimulation

Sub-threshold stimulation that does not activate neural structures.

Intervention Type OTHER

Other Intervention Names

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PAS VNS Sham

Eligibility Criteria

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Inclusion Criteria

INDIVIDUALS WHO HAVE HAD A STROKE:

1. Diagnosis of first ever stroke
2. At least 6 months after stroke onset
3. Motor-evoked potentials in hand/arm muscles
4. Subjects must show an understanding of the study goals and have the ability to follow simple directions as judged by the investigators.

ALL INDIVIDUALS:
5. Between the ages of 18 and 75 years old

Exclusion Criteria

INDIVIDUALS WHO HAVE HAD A STROKE:

1. Hemispatial neglect, aphasia, or cognitive impairment that would impact testing and would interfere with the ability to follow simple instructions, as judged by the investigators

ALL INDIVIDUALS:
2. Neurological disorder(s) influencing movement (besides stroke)
3. History of seizure or epilepsy
4. Metallic brain implants
5. Bodily implants such as cardioverter defibrillators, insulin pumps, ventriculoperitoneal shunts, cochlear implants, or pacemakers
6. Pregnant or expecting to become pregnant
7. Difficulty maintaining alertness and/or remaining still
8. Silicone or plastic allergy
9. History of vestibular disorders (eg, Vertigo, Meniere's Disease, etc.)
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Pittsburgh

OTHER

Sponsor Role lead

Responsible Party

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George Wittenberg

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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George F Wittenberg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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Nakayama H, Jorgensen HS, Raaschou HO, Olsen TS. Recovery of upper extremity function in stroke patients: the Copenhagen Stroke Study. Arch Phys Med Rehabil. 1994 Apr;75(4):394-8. doi: 10.1016/0003-9993(94)90161-9.

Reference Type BACKGROUND
PMID: 8172497 (View on PubMed)

Pollock A, St George B, Fenton M, Firkins L. Top ten research priorities relating to life after stroke. Lancet Neurol. 2012 Mar;11(3):209. doi: 10.1016/S1474-4422(12)70029-7. No abstract available.

Reference Type BACKGROUND
PMID: 22341029 (View on PubMed)

Langhorne P, Coupar F, Pollock A. Motor recovery after stroke: a systematic review. Lancet Neurol. 2009 Aug;8(8):741-54. doi: 10.1016/S1474-4422(09)70150-4.

Reference Type BACKGROUND
PMID: 19608100 (View on PubMed)

Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ; American Heart Association Advocacy Coordinating Committee; Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Arteriosclerosis; Thrombosis and Vascular Biology; Council on Cardiopulmonary; Critical Care; Perioperative and Resuscitation; Council on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease; Council on Cardiovascular Surgery and Anesthesia, and Interdisciplinary Council on Quality of Care and Outcomes Research. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011 Mar 1;123(8):933-44. doi: 10.1161/CIR.0b013e31820a55f5. Epub 2011 Jan 24.

Reference Type BACKGROUND
PMID: 21262990 (View on PubMed)

Porter BA, Khodaparast N, Fayyaz T, Cheung RJ, Ahmed SS, Vrana WA, Rennaker RL 2nd, Kilgard MP. Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex. Cereb Cortex. 2012 Oct;22(10):2365-74. doi: 10.1093/cercor/bhr316. Epub 2011 Nov 10.

Reference Type BACKGROUND
PMID: 22079923 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23954448 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24553102 (View on PubMed)

Meyers EC, Solorzano BR, James J, Ganzer PD, Lai ES, Rennaker RL 2nd, Kilgard MP, Hays SA. Vagus Nerve Stimulation Enhances Stable Plasticity and Generalization of Stroke Recovery. Stroke. 2018 Mar;49(3):710-717. doi: 10.1161/STROKEAHA.117.019202. Epub 2018 Jan 25.

Reference Type BACKGROUND
PMID: 29371435 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26645257 (View on PubMed)

Kilgard MP, Rennaker RL, Alexander J, Dawson J. Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient. NeuroRehabilitation. 2018;42(2):159-165. doi: 10.3233/NRE-172273.

Reference Type BACKGROUND
PMID: 29562561 (View on PubMed)

Kimberley TJ, Pierce D, Prudente CN, Francisco GE, Yozbatiran N, Smith P, Tarver B, Engineer ND, Alexander Dickie D, Kline DK, Wigginton JG, Cramer SC, Dawson J. Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke. Stroke. 2018 Nov;49(11):2789-2792. doi: 10.1161/STROKEAHA.118.022279.

Reference Type BACKGROUND
PMID: 30355189 (View on PubMed)

Other Identifiers

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STUDY19040394 (Aim 1)

Identifier Type: -

Identifier Source: org_study_id

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