Non-invasive Vagus Nerve Stimulation for Parkinson's Disease (VNS)

Although breakthroughs in the management of Parkinson's disease (PD) have emerged in recent decades resulting in better control in symptoms, majority of patients with PD are still living with various disabling motor and non-motor symptoms despite they are already receiving the best contemporary medical or surgical treatments available to them. There is obviously a need to develop additional treatment modality to further optimize the control of symptoms and/or slow the disease progression for patients having PD.

Vagus nerve stimulation (VNS), a type of noninvasive brain stimulation is believed to modify brain rhythms by modulating the nucleus of the solitary tract and locus coeruleus and other regions known to play a role in gait. Moreover, VNS may modulate inflammatory pathways and reduce oxidative stress, making it a potential disease modifying treatment approach for neurodegenerative diseases linked to neuroinflammation such as PD

Further study is warranted to explore the efficacy of non-invasive VNS for its effects on gait and other symptoms of PD as well as the anti-inflammatory effects.

Study Overview

• Status: Not yet recruiting
• Conditions: Idiopathic Parkinson Disease
• Intervention / Treatment: Device: cVNS; Device: eVNS; Device: sVNS

Detailed Description

The objective of the present study is to investigate the feasibility, safety, and potential efficacy of 2 different non-invasive VNS stimulation protocols (conventional and exploratory) for patients with PD. The immediate effects of VNS as well as the medium-term effects of daily VNS at 2 and 4 weeks poststimulation, and the delayed effects of non-invasive VNS at 8 weeks of both stimulation protocols will be investigated. The effects of non-invasive VNS of the 2 different stimulation protocols will also be compared with sham stimulation. The study will be a randomized single blind study. The tested subjects, not the assessor, will be kept unaware of which treatment protocols they are receiving.

The investigator hypothesize the VNS stimulations may provide immediate effects, medium term effects and delayed effects.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pauline Kwan, Master's Degree; Phone Number: +852 26352160; Email: paulinekwan@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Idiopathic PD as defined by the UK Parkinson's Disease Society Brain Bank Diagnostic Criteria

2. Age 40 - 75 years old

3. Presence of gait impairment as defined by any one of the below:

   a UPDRS Part 2 Item 15 (Walking) with a score of 2 b. UPDRS Part 3 Item 26 (leg Agility) with score of 2 or 3 c. UPDRS Part 3 Item 29 (Gait) with score of 1 or 2

4. Availability of a caregiver at home

5. Cantonese speaker

Exclusion Criteria:

1. Patients with atypical parkinsonism (e.g., multiple system atrophy, progressive supranuclear palsy, dementia with Lewy Bodies)
2. PD with dementia
3. PD patients with DBS in-situ
4. Severe PD with a Hoehn and Yahr staging of 4 or above
5. Low blood pressure with systolic of < 110 mmHg or with postural hypotension as defined by a decrease in systolic and diastolic blood pressure by 20 mmHg and 10mmHg upon standing, respectively)
6. Cardiac pacemaker in-situ

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: conventional VNS; Parkinson Disease	Device: cVNS; The cVNS emits a low-voltage 5.56 KHz sinusoidal wave electrical signal bursts lasting 0.9 ms via two flat stimulation contact surfaces. (Figure 2) These bursts repeat once every 38 millisecond (ms). Each set of stimulation will be applied for 2 minutes. Stimulation current can be self-adjusted by the subject. This conventional stimulation waveform was approved by the US FDA for the treatment of migraines.
Active Comparator: exploratory VNS	Device: eVNS; The eVNS emits the company-proprietary low-voltage of 3~8 KHz sine-variant smooth-transition wave electrical signal bursts lasting near 0.9 ms via two flat stimulation contact surfaces. These bursts repeat once in intervals of approximately 40 ms. A potential benefit of this waveform is that it can produce less unpleasant skin sensations at a given current intensity and this may enhance the subject to tolerate higher current intensity than that of the conventional stimulation.
Sham Comparator: sham VNS	Device: sVNS; The sVNS delivers mechanical motor vibrations to provide a similar perceptible stimulation feeling to the skin. No electrical stimulations are delivered. The device that delivers the sham stimulation is identical in appearance, weight, and user interface. A button to adjust "stimulation current" is also available in the sham device so as to allow the subject/caregiver to adjust the "stimulation current"

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of gait	Timed UP and Go test: Participant sits back in a standard armchair with their back against the chair and hands resting on the armrests. Regular footwear and usual walking aids (like a cane or walker) are used. On the word "Go", the person stands up, walks a distance of 3 meters (10 feet) to a marked line or cone at a normal, safe pace, turns around, walks back to the chair, and sits down again. A stopwatch starts the moment the word "Go" is spoken and stops the moment the person's buttocks touch the seat. The results in second will be interpret to assist mobility and risk of falling. The longer the time, the high risk of fall	Baseline, Day 1 stimulation visit, 4 week post-home stimulation visits and 8 week post-home stimulation visits
Severity and progression of Parkinson's disease	Using Unified Parkinson's Disease Rating Scale to motor and non-motor symptoms. Score from 0 to 4. 0 is normal while 4 is severe/marked impairment	Baseline, Day 1 stimulation visit, 4 week post-home stimulation visits and 8 week post-home stimulation visits
Quantitative Gait Assessment	Using an app to track the mobility of participants in a 20 sec walking	Baseline, Day 1 stimulation visit, 4 week post-home stimulation visits and 8 week post-home stimulation visits
Cognitive status	Using Hong Kong Montreal Cognitive Assessment to evaluate the cognitive status. score from 0-30. The lower the score, the more cognitive impaired.	Baseline, Day 1 stimulation visit, 4 week post-home stimulation visits and 8 week post-home stimulation visits
Change in mood	Using Geriatric depression scale which contain 15 questions. Score from 0-15. The higher the score, the more severe the depressed mood	Baseline, Day 1 stimulation visit, 4 week post-home stimulation visits and 8 week post-home stimulation visits

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of blood pressure		Baseline, Day 1 stimulation visit, 4 week post-home stimulation visits and 8 week post-home stimulation visits
Safety measures- record of adverse event and serious adverse event	To investigate any possibility and relativity of AE and SAE with the treatment	Baseline, Day 1 stimulation visit, 4 week post-home stimulation visits and 8 week post-home stimulation visits
Electrocardiogram	To investigate any possibility and relativity of the change of ECG with the treatment	Baseline, Day 1 stimulation visit, 4 week post-home stimulation visits and 8 week post-home stimulation visits

Other Outcome Measures

Outcome Measure	Time Frame
Blood-based biomarkers	Baseline, Day 1 stimulation visit, 4 week post-home stimulation visits and 8 week post-home stimulation visits

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Publications and helpful links

General Publications

• Castro JI, Valencia Llano CH, Tenorio DL, Saavedra M, Zapata P, Navia-Porras DP, Delgado-Ospina J, Chaur MN, Hernandez JHM, Grande-Tovar CD. Biocompatibility Assessment of Polylactic Acid (PLA) and Nanobioglass (n-BG) Nanocomposites for Biomedical Applications. Molecules. 2022 Jun 6;27(11):3640. doi: 10.3390/molecules27113640.
• Eissazade N, Eghdami S, Rohani M, Ajdari A, Fereshtehnejad SM, Fasano A, Khoeini T. Noninvasive Vagus Nerve Stimulation in Parkinson's Disease: A Systematic Review. Neuromodulation. 2025 Jun;28(4):641-651. doi: 10.1016/j.neurom.2025.01.012. Epub 2025 Mar 6.
• Mondal B, Choudhury S, Banerjee R, Roy A, Chatterjee K, Basu P, Singh R, Halder S, Shubham S, Baker SN, Baker MR, Kumar H. Effects of non-invasive vagus nerve stimulation on clinical symptoms and molecular biomarkers in Parkinson's disease. Front Aging Neurosci. 2024 Feb 7;15:1331575. doi: 10.3389/fnagi.2023.1331575. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Estimated): November 20, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: September 22, 2026
• First Submitted That Met QC Criteria: October 28, 2026
• First Posted (Actual): November 2, 2026

Study Record Updates

• Last Update Posted (Actual): November 3, 2026
• Last Update Submitted That Met QC Criteria: November 2, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: 2025.519

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

only IPD used in the results publication will be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No