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The goal of this clinical trial is to learn if stimulating the vagus nerve in combination with a motor task in people with multiple sclerosis can improve motor function. The main questions it aims to answer are:
Researchers will compare active vagus nerve stimulation to a sham stimulation to see if the paired vagus nerve stimulation can improve motor control.
Participants will:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental - Active Stimulation | Experimental | Participants in this arm will receive active stimulation during the paired motor task. |
|
| Control - Sham Stimulation | Sham Comparator | Participants in this arm will receive sham stimulation during the paired motor task to create a control to the experimental group. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Closed Loop Trans-Auricular Vagus Nerve Stimulation System | Device | A closed loop system that delivers stimulation to the vagus nerve via the ear non-invasively following a trigger event. |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of adverse events in response to paired-taVNS treatment | The frequency of adverse events (AEs) or serious adverse events (SAEs) will be monitored during the 6-month paired-taVNS treatment to measure the safety and tolerance of the intervention. | End of Study (6 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in time to complete the grooved peg test | The participant will complete the grooved peg test with their dominant hand and will be timed while doing so. The change in time to completion will be tracked over the study. | End of Study (6 months) |
| Change from baseline of score of the upper extremity portion of the Fugl-Meyer Assessment |
| Measure | Description | Time Frame |
|---|---|---|
| Change in mean magnetization transfer resonance (MTR) signal in white matter (WM) lesions from baseline to 6 months | Changes in MTR will be evaluated as an exploratory imaging measure of tissue repair and remyelination. | End of Study (6 months) |
| Change in the 25th percentile of the normalized proton density-weighted MRI lesion signal (nPD2574) from baseline to 6 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Bennett, MD | Anschutz Campus - School of Medicine - Neurology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Translational Research Center at CU Anschutz | Aurora | Colorado | 80010 | United States |
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| Placebo | Device | A closed-loop vagus nerve stimulation device that can deliver sham stimulation to the ear to simulate stimulation of the vagus nerve. |
|
The upper extremity portion of the Fugl-Meyer assessment evaluates movements of the upper limbs with score ranging from 0 - 66. A higher score indicates more function. |
| End of Study (6 months) |
| Change from baseline score of the Expanded Disability Status Scale | The expanded disability status scale scores range from 0 - 10, where 10 indicates full function. | End of Study (6 months) |
| Change in time from baseline to complete the timed 25 foot walk test | The timed 25 foot walk test is a performance measure where the participants walks 25 feet unassisted and the time to completion is recorded. | End of Study (6 months) |
| Change from baseline in composite disability metric | The fraction of participants in each intervention group at 6 months with improvement in disability will be determined by a composite disability metric composed of three elements: expanded disability status scale, timed 25 foot walk, and grooved peg test time. The metric will be deemed positive if there is a significant change in one or more of the measures as determined as follows: 1) decrease in expanded disability status scale score of 1 point (baseline expanded disability status scale score ≤5.5) or 0.5 point (baseline expanded disability status scale score of >5.5); 2) 20% decrease in timed 25 foot walk test; or 3) 25% decrease in grooved peg test time. The composite disability metric will be quantified by a trained study personnel. | End of Study (6 months) |
| Change in Dellon-Modified Moberg Pick-Up Test | Dellon-Modified Moberg Pick-Up Test (DMMPUT) is a test requiring the pickup of small objects commonly used in everyday life. The change in time for completion will be tracked for the duration of the study. | End of Study (6 months) |
| Change from baseline in patient reported outcomes from the multiple sclerosis impact scale 29 | The Multiple Sclerosis Impact Scale - 29 is a 29-item patient-reported measure of the physical and psychological impacts of multiple sclerosis. Participants are asked to rate how much their functioning and well-being has been impacted over the past 14 days on a 4-point scale. Higher scores indicate a greater disease impact. | End of Study (6 months) |
| Motor Evoked Potential | The Motor Evoked Potential will evaluate conduction through the corticospinal pathways. | End of Study (6 months) |
| Visual Evoked Potential | The Visual Evoked Potential will evaluate conduction through the visual pathways. | End of Study (6 months) |
Changes in nPD25 will be evaluated as an exploratory imaging measure of tissue repair and remyelination. |
| End of Study (6 months) |
| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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