NCT04088565

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
26

participants targeted

Target at P25-P50 for not_applicable stroke

Timeline
Completed

Started Sep 2019

Typical duration for not_applicable stroke

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 9, 2019

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 13, 2019

Completed
9 days until next milestone

Study Start

First participant enrolled

September 22, 2019

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 9, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 9, 2021

Completed
Last Updated

November 1, 2022

Status Verified

October 1, 2022

Enrollment Period

2.1 years

First QC Date

September 9, 2019

Last Update Submit

October 31, 2022

Conditions

Stroke

Keywords

NeuromodulationParesisNeurorehabilitation

Outcome Measures

Primary Outcomes (1)

  • Change in size of evoked potential

    The primary endpoint is the change from baseline (ie, before PAS) in the size of evoked potentials. Differences in the change between conditions (ie, PAS+VNS vs PAS+Sham) will address whether VNS drives cortical plasticity.

    1 week

Study Arms (2)

PAS+VNS

EXPERIMENTAL

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.

Other: Paired-Associative Stimulation (PAS)Other: Vagus Nerve Stimulation (VNS)

PAS+Sham

SHAM COMPARATOR

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.

Other: Paired-Associative Stimulation (PAS)Other: Sham Stimulation

Interventions

Paired-Associative Stimulation (PAS)OTHER

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

Also known as: PAS
PAS+ShamPAS+VNS
Vagus Nerve Stimulation (VNS)OTHER

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

Also known as: VNS
PAS+VNS
Sham StimulationOTHER

Sub-threshold stimulation that does not activate neural structures.

Also known as: Sham
PAS+Sham

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • INDIVIDUALS WHO HAVE HAD A STROKE:
  • Diagnosis of first ever stroke
  • At least 6 months after stroke onset
  • Motor-evoked potentials in hand/arm muscles
  • Subjects must show an understanding of the study goals and have the ability to follow simple directions as judged by the investigators.
  • ALL INDIVIDUALS:
  • Between the ages of 18 and 75 years old

You may not qualify if:

  • INDIVIDUALS WHO HAVE HAD A STROKE:
  • 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:
  • Neurological disorder(s) influencing movement (besides stroke)
  • History of seizure or epilepsy
  • Metallic brain implants
  • Bodily implants such as cardioverter defibrillators, insulin pumps, ventriculoperitoneal shunts, cochlear implants, or pacemakers
  • Pregnant or expecting to become pregnant
  • Difficulty maintaining alertness and/or remaining still
  • Silicone or plastic allergy
  • History of vestibular disorders (eg, Vertigo, Meniere's Disease, etc.)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (11)

  • 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.

    PMID: 8172497BACKGROUND

  • 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.

    PMID: 22341029BACKGROUND

  • 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.

    PMID: 19608100BACKGROUND

  • 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.

    PMID: 21262990BACKGROUND

  • 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.

    PMID: 22079923BACKGROUND

  • 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.

    PMID: 23954448BACKGROUND

  • 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.

    PMID: 24553102BACKGROUND

  • 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.

    PMID: 29371435BACKGROUND

  • 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.

    PMID: 26645257BACKGROUND

  • 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.

    PMID: 29562561BACKGROUND

  • 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.

    PMID: 30355189BACKGROUND

MeSH Terms

Conditions

StrokeParesis

Interventions

Vagus Nerve Stimulationsalicylhydroxamic acid

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation TherapyTherapeutics

Study Officials

  • George F Wittenberg, MD, PhD

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

September 9, 2019

First Posted

September 13, 2019

Study Start

September 22, 2019

Primary Completion

November 9, 2021

Study Completion

November 9, 2021

Last Updated

November 1, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will share

The research team may share data with scientists at other centers for the purpose of data analysis and collaboration. Research information and data may be shared with investigators conducting other research. This information will not be identifiable.

Shared Documents
STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
Time Frame
Information may be shared while data is being recorded, analyzed, and/or prior to publication. Data may be available for seven years after manuscripts are published.
Access Criteria
Data use agreements will be established with scientists at other centers, or conducting other research, prior to any data sharing.

Locations

US(1)