Paired Vagus Nerve Stimulation Mechanisms

NCT06716112 | Recruiting DMC FDA Device

• 1 other identifier: 24-00751
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

In this mechanistic study, 40 individuals with chronic stroke will be implanted with a small vagus nerve stimulation (VNS) device. The study will use a randomized, blinded, crossover design to deliver two conditions in six-week blocks: active VNS or sham VNS, each paired with upper extremity (UE) motor rehabilitation. Assessment visits will occur before and after each block, and will examine neural pathway strength, functional connectivity, and motor and non-motor behaviors. Investigators will test for VNS-induced changes in motor, cognitive, and affective systems, and will identify biomarkers predictive of clinical response.

Conditions

Chronic Stroke

Outcome Measures

Primary Outcomes (2)

• Percent change in Ipsilesional CST MEP Size after Active VNS

  Ipsilesional corticospinal tract (CST) motor evoked potential (MEP) size measured before and after the treatment block.

  Pre-Active VNS Treatment Block (Week 0 [Arm 1] or Week 6 [Arm 2]), Post-Active VNS Treatment Block (Week 6 [Arm 1] or Week 12 [Arm 2])

• Percent change in Ipsilesional CST MEP Size after Sham VNS

  Ipsilesional corticospinal tract (CST) motor evoked potential (MEP) size measured before and after the treatment block.

  Pre-Sham VNS Treatment Block (Week 0 [Arm 2] or Week 6 [Arm 1]), Post-Sham VNS Treatment Block (Week 6 [Arm 2] or Week 12 [Arm 1])

Secondary Outcomes (8)

• Percent change in Ipsilesional CReST MEP Size after Active VNS

  Pre-Active VNS Treatment Block (Week 0 [Arm 1] or Week 6 [Arm 2]), Post-Active VNS Treatment Block (Week 6 [Arm 1] or Week 12 [Arm 2])

• Percent change in Ipsilesional CReST MEP Size after Sham VNS

  Pre-Sham VNS Treatment Block (Week 0 [Arm 2] or Week 6 [Arm 1]), Post-Sham VNS Treatment Block (Week 6 [Arm 2] or Week 12 [Arm 1])

• Percent Change in Arm Strength after Active VNS

  Pre-Active VNS Treatment Block (Week 0 [Arm 1] or Week 6 [Arm 2]), Post-Active VNS Treatment Block (Week 6 [Arm 1] or Week 12 [Arm 2])

• Percent Change in Arm Strength after Sham VNS

  Pre-Sham VNS Treatment Block (Week 0 [Arm 2] or Week 6 [Arm 1]), Post-Sham VNS Treatment Block (Week 6 [Arm 2] or Week 12 [Arm 1])

• Percent Change in Motor Control after Active VNS

  Pre-Active VNS Treatment Block (Week 0 [Arm 1] or Week 6 [Arm 2]), Post-Active VNS Treatment Block (Week 6 [Arm 1] or Week 12 [Arm 2])

Study Arms (2)

Active VNS first, then Sham VNS

EXPERIMENTAL

Patients will undergo two 6-week intervention blocks, receiving active VNS first and sham VNS second. Blocks consist of three 90-minute sessions per week with a licensed occupational therapist (OT). During these sessions, patients will perform rehabilitation training activities paired with active VNS during the first block and paired with sham VNS during the second block.

Device: Vagus Nerve Stimulation (VNS) Device; Device: Sham VNS Device; Behavioral: Upper Extremity Rehabilitation

Sham VNS first, then Active VNS

EXPERIMENTAL

Patients will undergo two 6-week intervention blocks, receiving sham VNS first and active VNS second. Blocks consist of three 90-minute sessions per week with a licensed occupational therapist (OT). During these sessions, patients will perform rehabilitation training activities paired with sham VNS during the first block and paired with active VNS during the second block.

Device: Vagus Nerve Stimulation (VNS) Device; Device: Sham VNS Device; Behavioral: Upper Extremity Rehabilitation

Interventions

Vagus Nerve Stimulation (VNS) Device DEVICE

All patients will be implanted with the ReStore VNS device by an NYU neurosurgeon. During treatment sessions, study personnel will deliver a VNS burst at the completion of a training movement by pressing a button on a smart device, which wirelessly triggers active VNS stimulation.

Active VNS first, then Sham VNS; Sham VNS first, then Active VNS

Sham VNS Device DEVICE

All patients will be implanted with the ReStore VNS device by an NYU neurosurgeon. During treatment sessions, study personnel will deliver a VNS burst at the completion of a training movement by pressing a button on a smart device, which wirelessly triggers sham VNS stimulation.

Active VNS first, then Sham VNS; Sham VNS first, then Active VNS

Upper Extremity Rehabilitation BEHAVIORAL

Rehabilitation training will be functional and activity-based, focusing on six task categories: reaching and grasping objects, gross movements with objects, flipping objects, inserting objects, self-feeding, and opening and closing containers. Three 90-minute training sessions per week will be administered by a licensed occupational therapist, over two six-week treatment blocks. Sessions will be paired with either active or sham VNS administration.

Active VNS first, then Sham VNS; Sham VNS first, then Active VNS

Eligibility Criteria

• Age: 22 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• years of age
• Unilateral supratentorial ischemic stroke that occurred ≥ 12 months prior to enrollment
• Upper extremity Fugl-Meyer Assessment score of 20 to 50
• Modified Rankin Score of 2, 3, or 4
• Meets all clinical criteria for VNS implantation as determined by the PI and clinical care team

You may not qualify if:

• Intracerebral hemorrhage or traumatic brain injury
• Deficits in language or attention that interfere with study participation
• Severe spasticity (Modified Ashworth \> 3)
• Psychiatric disorders and/or cognitive impairments that would interfere with study participation, as assessed by medical evaluation
• Receiving any therapy (medication or otherwise) that would interfere with VNS, such as drugs that perturb neurotransmitter action (anticholinergics, adrenergic blockers, etc.)
• Presence of any other implanted electrical stimulation device
• Prior injury to vagus nerve
• Females of childbearing potential who are either pregnant, lactating, heterosexually active, or planning to become pregnant or heterosexually active during study participation; and who are not using, or will not agree to use, the following medically acceptable birth control methods:\* (1) sterilization surgery for women, (2) Surgical Sterilization Implant for Women, (3) sterilization surgery for men, (4) long-acting reversible contraceptives (LARC) - implantable rod and IUD; (5) contraceptive shot/injection every 3 months; (6) oral contraceptives ("The Pill"); (7) contraceptive patch; and (8) vaginal contraceptive ring.
• Concurrent participation in another interventional clinical trial
• Ferromagnetic metal in head (except dental work) or torso
• Persons with a current or past: (a) medical (psychiatric, non-psychiatric) condition, disease, disorder, injury, or disability\*; or (b) non-medical situation or circumstance that, in the opinion of the principal investigator, study participation: may pose a significant or undue risk to the person; make it unlikely the person will complete all the study requirements per protocol; or may adversely impact the integrity of the data or the validity of the study results. \[\*Examples include, but are not limited to, the following types of conditions, diseases or disorders: renal, peripheral vascular, cardiac, endocrinologic (e.g., diabetes), immunologic, psychiatric (e.g., substance use), neurologic (e.g., cognitive), or dysphagia\]
• Persons with a neck circumference larger than 18.5 inches
• As determined by the principal investigator, is under current incarceration or legal detention

Sponsors & Collaborators

• NYU Langone Health: lead
• National Institutes of Health (NIH): collaborator
• The University of Texas at Dallas: collaborator

Study Sites (2)

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

The University of Texas at Dallas

Richardson, Texas, 75080, United States

RECRUITING

MeSH Terms

Interventions

Vagus Nerve Stimulation

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Officials

• Heidi Schambra, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heidi Schambra

CONTACT

929-455-5128; Heidi.schambra@nyulangone.org

Study Design

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

Study Record Dates

• First Submitted: November 29, 2024
• First Posted: December 4, 2024
• Study Start: July 15, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Heidi.schambra@nyulangone.org. To gain access, data requestors will need to sign a data access agreement. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's DSSB.

Locations

US (2)