Mechanisms of Paired Vagus Nerve Stimulation (VNS) in Chronic Stroke: a Randomized, Blinded, Sham-controlled, Single-center Mechanistic Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Terminated
- Sponsor
- NYU Langone Health
- Enrollment
- 4
- Locations
- 2
- Primary Endpoint
- Percent change in Ipsilesional CST MEP Size after Active VNS
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 22 Years to 79 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •22-79 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
Exclusion Criteria
- •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
Arms & Interventions
Active VNS first, then Sham VNS
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.
Intervention: Upper Extremity Rehabilitation (Behavioral)
Sham VNS first, then Active VNS
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.
Intervention: Vagus Nerve Stimulation (VNS) Device (Device)
Active VNS first, then Sham VNS
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.
Intervention: Vagus Nerve Stimulation (VNS) Device (Device)
Active VNS first, then Sham VNS
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.
Intervention: Sham VNS Device (Device)
Sham VNS first, then Active VNS
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.
Intervention: Sham VNS Device (Device)
Sham VNS first, then Active VNS
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.
Intervention: Upper Extremity Rehabilitation (Behavioral)
Outcomes
Primary Outcomes
Percent change in Ipsilesional CST MEP Size after Active VNS
Time Frame: 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])
Ipsilesional corticospinal tract (CST) motor evoked potential (MEP) size measured before and after the treatment block.
Percent change in Ipsilesional CST MEP Size after Sham VNS
Time Frame: 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])
Ipsilesional corticospinal tract (CST) motor evoked potential (MEP) size measured before and after the treatment block.
Secondary Outcomes
- 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 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]))
- Percent Change in Motor Control 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 Individuation 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 Individuation 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 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]))
- Percent Change in Motor Control 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 Individuation 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 Individuation 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]))