Non-invasive VNS for PD Gait

NCT ID: NCT06562569

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-09
• Study Completion Date: 2027-04-01

Brief Summary

More than 110,000 US Veterans living with Parkinson's disease (PD) currently receive PD-related care and services from the VA. Fall prevention is a priority for Veterans living PD. Gait disturbances are a major cause for functional dependence and the largest risk factor for falls, institutionalization, and death in PD. This SPiRE addresses the need to advance nonpharmacological rehabilitative health care of Veterans and maximizing functional outcomes by developing a non-invasive, neuromodulatory transcutaneous cervical Vagal Nerve Stimulation as an at-home intervention to improve gait and balance. This pilot clinical trial will assist with future efforts and priorities of the VA to prolong independent living and quality of life by minimizing gait and balance dysfunction experienced by Veterans living with PD.

Detailed Description

More than 110,000 US Veterans living with Parkinson's disease (PD) currently receive PD-related care and services from the VA. PD is a complex chronic neurodegenerative multisystem disorder. Fall prevention is a priority for Veterans living with PD. Gait disturbances are a major cause for functional dependence and the largest risk factor for falls, institutionalization, and death in PD. Gait abnormalities are evident at the time of PD diagnosis and are one of the most disabling features of PD. They are also difficult aspects to treat as pharmacologic agents do not address the entire spectrum of gait abnormalities. Overall management of PD symptoms can be challenging due to pharmacological interactions and drug side effects. Developing a non-pharmacological and non-invasive therapeutic to improve gait and balance is a critical need for Veterans with PD who are managing complex chronic conditions. Moreover, advancing at-home rehabilitation is ideal for a population of geriatric Veterans who are facing mobility issues, managing multiple chronic conditions and who rely on caregiver support. Non-invasive cervical Vagal Nerve Stimulation (ncVNS) may be a solution. ncVNS is currently licensed to treat and prevent migraine and other headache syndromes and is covered by the VAH for these indications. ncVNS can be self-administered, daily, at home. A hand-held device is used to make contact to the left side of the neck so that the vagal nerve is stimulated. ncVNS decreases inflammation and oxidative stress through activation of the cholinergic anti-inflammatory pathway, which in turn can contribute to gait improvements in PD. One of the most debilitating gait deficits in PD is Freezing of Gait (FOG), an episodic failure to initiate or maintain walking, especially while turning. Given that FOG, along with falls, is related to cholinergic dysfunction, both might be reduced following ncVNS. Exciting, but limited research over the past decade indicates this neuromodulatory approach has the potential to improve gait features in PD. The objectives of this SPiRE are to develop a framework for an at-home ncVNS intervention, develop an appropriate control intervention for a future larger study and gather preliminary clinical outcome data on PD-specific features. The central hypotheses are that (i) a 4 week at-home active ncVNS intervention and a sham ncVNS control condition will be acceptable and feasible to complete and (ii) active ncVNS compared to both control ncVNS and treatment as usual (TAU), will lead to greater improvements in gait, FOG, balance and fall frequency. The proposed study is a pilot, prospective parallel group randomized control trial (RCT). Twenty participants will be randomized to 4 weeks of either active (n=10) or sham ncVNS (n=10). A third group (n=10) will not receive ncVNS but will continue with their treatment as usual (TAU). The investigators will examine acute, cumulative, and sustainable effects of ncVNS. Advancing non-pharmacologic treatments to improve gait dynamics is a critical need for Veterans with PD. Moreover, advancing at-home rehabilitation is ideal for a population of geriatric Veterans who are facing multiple issues including mobility. This SPiRE is strongly aligned with VA priorities to advance rehabilitative health care of Veterans and restore their physical function to improve QoL. If the aims are achieved, the investigators will have completed necessary first steps towards developing an at-home easy to use, neuromodulatory intervention that should translate to improved gait and balance and contribute to fewer falls. This project will yield preliminary data to support a VA Merit and move forward not only the field of noninvasive and nonpharmacological interventions for PD rehabilitation but also the general field of gait and balance rehabilitation.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group 1

Vagal nerve stimulation at an intensity under 10 units. Participants will self-administered at this intensity for 2 minutes each day over 4 weeks.

Group Type: EXPERIMENTAL

non-invasive cervical vagal nerve stimulation ncVNS

Intervention Type: DEVICE

The ncVNS device is a rechargable, handheld device that generate a proprietary frequency-modulated electrical stimulus at low voltage (max 24V) with a max current output of 60mA. The signal consists of 1ms bursts of 5kHz sine waves repeated at 25Hz. Two stainless steel contact surfaces coated with conductive gel deliver the stimulus to the neck in the vicinity of the vagus nerve.

Group 2

Vagal nerve stimulation at the highest intensity tolerated by the participant. Participants will self-administered at this intensity for 12 minutes each day over 4 weeks.

Group Type: EXPERIMENTAL

non-invasive cervical vagal nerve stimulation ncVNS

Intervention Type: DEVICE

The ncVNS device is a rechargable, handheld device that generate a proprietary frequency-modulated electrical stimulus at low voltage (max 24V) with a max current output of 60mA. The signal consists of 1ms bursts of 5kHz sine waves repeated at 25Hz. Two stainless steel contact surfaces coated with conductive gel deliver the stimulus to the neck in the vicinity of the vagus nerve.

Group 3

This group will not receive any stimulation. Participants will receive their treatment as usual.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

non-invasive cervical vagal nerve stimulation ncVNS

The ncVNS device is a rechargable, handheld device that generate a proprietary frequency-modulated electrical stimulus at low voltage (max 24V) with a max current output of 60mA. The signal consists of 1ms bursts of 5kHz sine waves repeated at 25Hz. Two stainless steel contact surfaces coated with conductive gel deliver the stimulus to the neck in the vicinity of the vagus nerve.

Intervention Type: DEVICE

Other Intervention Names

VNS

Eligibility Criteria

Inclusion Criteria

• Parkinson's disease, as diagnosis by a VA neurologist
• HY stages 2-3
• Self-report Freezing of Gait
• Able to ambulate for 2-min without an assistive device
• Parkinson's disease medications are stable for 4-weeks and expected to be on stable medications for duration of the study

Exclusion Criteria

• Lack of decision-making capacity
• Prescribed centrally acting anticholinergics (e.g., amitriptyline) or cholinesterase inhibitors
• Musculoskeletal or additional neurological conditions that negatively impact gait and balance
• Spine or LE surgery within the past year
• Known or suspected:

• severe atherosclerotic cardiovascular disease
• severe carotid artery disease
• congestive heart failure
• known severe coronary artery disease or prior myocardial infarction
• Abnormal baseline electrocardiogram within last year
• Previous vagotomy
• Implanted metal cervical spine hardware, other metallic implants or implantable medical devices such as DBS
• History of syncope or seizures (within the last 2 years)

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 88 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandra L. Kletzel, PhD BA

Role: PRINCIPAL_INVESTIGATOR

Edward Hines Jr. VA Hospital, Hines, IL

Locations

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, United States

Countries

United States

Central Contacts

Sandra L Kletzel, PhD BA

Role: CONTACT

Sandra.Kletzel@va.gov

(708) 202-5735

Alexandria N Umbarger, BS

Role: CONTACT

alexandria.umbarger@va.gov

(708) 998-8213

Facility Contacts

William Wolf, PhD

Role: primary

William.Wolf@va.gov

(708) 202-5689

Other Identifiers

E5133-P

Identifier Type: -

Identifier Source: org_study_id