VNS-induced Corticospinal Plasticity

Stroke Clinical Trial

Official title:

Mechanisms of Non-invasive Vagus Nerve Stimulation Underlying Enhanced Motor Control in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04088565
• Other study ID #: STUDY19040394 (Aim 1)
• Status: Completed
• Phase: N/A
• Start date: September 22, 2019
• Est. completion date: November 9, 2021

Study information

• Verified date: October 2022
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: November 9, 2021
• Est. primary completion date: November 9, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.)

Related Conditions & MeSH terms

• Stroke

Intervention

Other:
• Paired-Associative Stimulation (PAS)
Simultaneous activation of connections in motor cortex via stimulation to the nerves and brain.
• Vagus Nerve Stimulation (VNS)
Recruits the auricular branch of the vagus nerve which activates brain structures that release chemicals mediating cortical plasticity.
• Sham Stimulation
Sub-threshold stimulation that does not activate neural structures.

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pittsburgh

Country where clinical trial is conducted

United States, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Nakayama H, Jørgensen 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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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