Effects of Vagal Nerve Stimulation on Leg Muscle Activity and Posture in Parkinson's Disease

NCT07226284 | Recruiting FDA Device

• 1 other identifier: NEUR-2025-34303
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to better understand the mechanisms contributing to impaired activation of leg muscles in people with Parkinson's disease (PD) and to test if stimulation of a nerve at the neck can improve muscle activation, walking and balance.

Conditions

Parkinson's Disease (PD); PARKINSON DISEASE (Disorder)

Keywords

nVNS; Vagus nerve; VNS; Parkinson's disease; PD; gammaCore

Outcome Measures

Primary Outcomes (1)

• Change in delta-F

  Difference between baseline and post-VNS delta-F measure

  Within-session VNS: 0-60 minutes. Between VNS sessions: 1 - 4 weeks.

Secondary Outcomes (4)

• Change in Braceheight

  Within-session VNS: 0 -60 minutes; between VNS sessions: 1-4 weeks

• Step length

  Within-session VNS: 0-60 minutes; between VNS sessions: 1-4 weeks

• Peak magnitude force on step leg

  Within-session VNS: 0-60 minutes; between VNS sessions: 1-4 weeks

• Postural sway magnitude

  Within-session VNS: 0-60 minutes; between VNS sessions: 1-4 weeks

Study Arms (3)

Baseline (no VNS)

OTHER

Within-subject and cross-sectional design that consists of 30 participants with PD (15 with PIGD and 15 without PIGD) and 15 matched controls.

Other: No intervention

Real nVNS

EXPERIMENTAL

Device: Vagal nerve stimulation

Sham nVNS

SHAM COMPARATOR

Sham VNS will be applied using setting that do not active the vagus nerve.

Other: No intervention

Interventions

No intervention OTHER

No nVNS is applied in the baseline experiment. Sham nVNS is applied for experiment two

Baseline (no VNS); Sham nVNS

Vagal nerve stimulation DEVICE

The gammaCore non-invasive vagus nerve stimulator (nVNS) is a hand-held portable device that is used to apply electrical stimulation to the vagus nerve via two electrodes.

Real nVNS

Eligibility Criteria

• Age: 21 Years - 76 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of idiopathic Parkinson's disease,
• On stable medication for the preceding month and anticipated over the next 3 months,
• Able to ambulate without the use of an assistive device for more than 50 meters.
• Control Cohort:
• Age (± 3 years) and sex distribution matched to the PD cohort,
• Able to ambulate without the use of an assistive device for more than 50 meters.

You may not qualify if:

• Failure to demonstrate capacity to consent (based on UBACC and/or MacArthur-CR),
• History of significant neurological disorder (besides PD in the PD group),
• History of stroke, traumatic brain injury, intracranial aneurysm, intracranial hemorrhage, brain tumor or atypical parkinsonian disorder,
• Severe orthopedic or other related musculoskeletal pathology that has significant adverse effects on gait,
• Women who are pregnant or may be pregnant,
• Insufficient comprehension of the English language,
• History of substance abuse in past 2 years;
• Pain at the nVNS treatment site (e.g., dysesthesia, neuralgia, cervicalgia);
• Lesion (including lymphadenopathy), previous surgery (including carotid endarterectomy or vascular neck surgery) or abnormal anatomy at the stimulation site (open wound, rash, infection, swelling, cut, sore, drug patch, surgical scar\[s\]);
• Known or suspected severe atherosclerotic cardiovascular disease, severe carotid artery disease (e.g., bruits or history of TIA or stroke), congestive heart failure, known severe coronary artery disease or prior myocardial infarction;
• Abnormal baseline electrocardiogram (ECG) within the last year (e.g., second or third-degree heart block, prolonged QT interval, atrial fibrillation, atrial flutter, history of ventricular tachycardia or ventricular fibrillation);
• Recent history of uncontrolled high blood pressure, bradycardia, tachycardia, or know recent history orthostatic hypotension;
• Previous unilateral or bilateral vagotomy;
• Implanted metal cervical spine hardware, other metallic implants or implantable medical devices such as deep brain stimulator, hearing aid implant, pacemaker, implanted cardioverter defibrillator, cranial aneurysm and/or cranial aneurysm clips, history of facial/orbital/metallic fragments, implanted electronic device, neurostimulator, valve replacements/stents, metallic implants/prostheses) near the stimulation site such as a bone plate or bone screw;
• History of syncope or seizures (within the last 2 years);

Sponsors & Collaborators

• Parkinson's Foundation: collaborator
• University of Minnesota: lead

Study Sites (1)

Movement Disorders Laboratory

Minneapolis, Minnesota, 55414, United States

RECRUITING

Related Publications (18)

• Mondal B, Choudhury S, Simon B, Baker MR, Kumar H. Noninvasive vagus nerve stimulation improves gait and reduces freezing of gait in Parkinson's disease. Mov Disord. 2019 Jun;34(6):917-918. doi: 10.1002/mds.27662. Epub 2019 Mar 14. No abstract available.

  PMID: 30869809 BACKGROUND

• Morris R, Yarnall AJ, Hunter H, Taylor JP, Baker MR, Rochester L. Noninvasive vagus nerve stimulation to target gait impairment in Parkinson's disease. Mov Disord. 2019 Jun;34(6):918-919. doi: 10.1002/mds.27664. Epub 2019 Mar 19. No abstract available.

  PMID: 30889295 BACKGROUND

• Negro F, Muceli S, Castronovo AM, Holobar A, Farina D. Multi-channel intramuscular and surface EMG decomposition by convolutive blind source separation. J Neural Eng. 2016 Apr;13(2):026027. doi: 10.1088/1741-2560/13/2/026027. Epub 2016 Feb 29.

  PMID: 26924829 BACKGROUND

• Stebbins GT, Goetz CG, Burn DJ, Jankovic J, Khoo TK, Tilley BC. How to identify tremor dominant and postural instability/gait difficulty groups with the movement disorder society unified Parkinson's disease rating scale: comparison with the unified Parkinson's disease rating scale. Mov Disord. 2013 May;28(5):668-70. doi: 10.1002/mds.25383. Epub 2013 Feb 13.

  PMID: 23408503 BACKGROUND

• Evancho A, Do M, Fortenberry D, Billings R, Sartayev A, Tyler WJ. Vagus nerve stimulation in Parkinson's disease: a scoping review of animal studies and human subjects research. NPJ Parkinsons Dis. 2024 Oct 24;10(1):199. doi: 10.1038/s41531-024-00803-1.

  PMID: 39448636 BACKGROUND

• Factor SA, Weinshenker D, McKay JL. A possible pathway to freezing of gait in Parkinson's disease. J Parkinsons Dis. 2025 Mar;15(2):282-290. doi: 10.1177/1877718X241308487. Epub 2025 Jan 14.

  PMID: 39973500 BACKGROUND

• Espay AJ, LeWitt PA, Kaufmann H. Norepinephrine deficiency in Parkinson's disease: the case for noradrenergic enhancement. Mov Disord. 2014 Dec;29(14):1710-9. doi: 10.1002/mds.26048. Epub 2014 Oct 9.

  PMID: 25297066 BACKGROUND

• Robichaud JA, Pfann KD, Comella CL, Brandabur M, Corcos DM. Greater impairment of extension movements as compared to flexion movements in Parkinson's disease. Exp Brain Res. 2004 May;156(2):240-54. doi: 10.1007/s00221-003-1782-0. Epub 2004 Jan 28.

  PMID: 14747885 BACKGROUND

• Pfann KD, Buchman AS, Comella CL, Corcos DM. Control of movement distance in Parkinson's disease. Mov Disord. 2001 Nov;16(6):1048-65. doi: 10.1002/mds.1220.

  PMID: 11748736 BACKGROUND

• Folland JP, Haas B, Castle PC. Strength and activation of the knee musculature in Parkinson's disease: effect of medication. NeuroRehabilitation. 2011;29(4):405-11. doi: 10.3233/NRE-2011-0719.

  PMID: 22207069 BACKGROUND

• Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003 Mar-Apr;24(2):197-211. doi: 10.1016/s0197-4580(02)00065-9.

  PMID: 12498954 BACKGROUND

• Kim EH, Wilson JM, Thompson CK, Heckman CJ. Differences in estimated persistent inward currents between ankle flexors and extensors in humans. J Neurophysiol. 2020 Aug 1;124(2):525-535. doi: 10.1152/jn.00746.2019. Epub 2020 Jul 15.

  PMID: 32667263 BACKGROUND

• Hulsey DR, Riley JR, Loerwald KW, Rennaker RL 2nd, Kilgard MP, Hays SA. Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation. Exp Neurol. 2017 Mar;289:21-30. doi: 10.1016/j.expneurol.2016.12.005. Epub 2016 Dec 14.

  PMID: 27988257 BACKGROUND

• Gorassini MA, Knash ME, Harvey PJ, Bennett DJ, Yang JF. Role of motoneurons in the generation of muscle spasms after spinal cord injury. Brain. 2004 Oct;127(Pt 10):2247-58. doi: 10.1093/brain/awh243. Epub 2004 Sep 1.

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• Johnson MD, Heckman CJ. Interactions between focused synaptic inputs and diffuse neuromodulation in the spinal cord. Ann N Y Acad Sci. 2010 Jun;1198:35-41. doi: 10.1111/j.1749-6632.2010.05430.x.

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• Heckman CJ, Mottram C, Quinlan K, Theiss R, Schuster J. Motoneuron excitability: the importance of neuromodulatory inputs. Clin Neurophysiol. 2009 Dec;120(12):2040-2054. doi: 10.1016/j.clinph.2009.08.009. Epub 2009 Sep 27.

  PMID: 19783207 BACKGROUND

• Smulders K, Dale ML, Carlson-Kuhta P, Nutt JG, Horak FB. Pharmacological treatment in Parkinson's disease: Effects on gait. Parkinsonism Relat Disord. 2016 Oct;31:3-13. doi: 10.1016/j.parkreldis.2016.07.006. Epub 2016 Jul 17.

  PMID: 27461783 BACKGROUND

• Kerr GK, Worringham CJ, Cole MH, Lacherez PF, Wood JM, Silburn PA. Predictors of future falls in Parkinson disease. Neurology. 2010 Jul 13;75(2):116-24. doi: 10.1212/WNL.0b013e3181e7b688. Epub 2010 Jun 23.

  PMID: 20574039 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Interventions

Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Central Study Contacts

Principal Investigator

CONTACT

612-625-8938; cmackinn@umn.edu

Kristin Garland

CONTACT

612-505-6574

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Experiment one will use both a within-subject and cross-sectional design and experiment two will be a double-blind crossover design.

Study Record Dates

• First Submitted: November 3, 2025
• First Posted: November 10, 2025
• Study Start: February 10, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)