Pupil-Indexed Noninvasive Neuromodulation

VA Office of Research and Development

Status: Enrolling

Conditions: Paresis

Treatments: Other: Transcutaneous Electrical Stimulation; Other: Sham

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT06282406

N4532-R

I0X1RX004532 (Other Grant/Funding Number)

Details and patient eligibility

About

Vagus nerve stimulation (VNS) is thought to activate neural pathways that release chemicals which promote plasticity and learning. Previous work has shown that the auricular branch of the vagus nerve innervates landmarks on the external ear. Work from the PI's laboratory has shown that electrical current applied to the external ear modulates physiological indexes of brain states implicated in the therapeutic effects of VNS. The broad objective of this project is to better understand physiological mechanisms modulated by auricular stimulation to support possible therapeutic effects in the form of motor learning.

Full description

Existing evidence supports the use of VNS to enhance the effects of traditional therapy on impairments due to neurological injury. It is known that the vagus nerve forms contacts with neuromodulatory nuclei in the brainstem that release of chemicals shown to be critically involved in attentional control and memory formation. It is also known that the auricular branch of the vagus nerve innervates portions of the external ear providing a possible means to engage similar neural pathways noninvasively via transcutaneous auricular vagus nerve stimulation (taVNS). Recent work from the PI's laboratory shows that electrical current applied to landmarks on the external ear elicits transient effects on pupil dilation, an established physiological index of brain states that support learning. Given the ability to engage the biomarker, the investigators aim to further investigate physiological mechanisms modulated by taVNS and possible effects on learning.

Enrollment: 110 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

ALL PROSPECTIVE SUBJECTS:

1. 18-75 years of age

   PROSPECTIVE SUBJECTS DIAGNOSED WITH STROKE:

2. Diagnosis of a single stroke resulting in hand impairment

3. Diagnosis of stroke at least six months prior to the time of participation

Exclusion criteria

ALL PROSPECTIVE SUBJECTS:

1. History of vestibular disorders or dizziness

2. Difficulty maintaining alertness and/or remaining still

3. Pregnant or expecting to become pregnant

4. Diagnosis of neurological and/or musculoskeletal disorder(s) (other than stroke) that affect movement

5. Ocular disease and/or impairment in more than one eye

6. History of seizure and/or epilepsy

7. Implants, devices, or foreign objects in the brain/body that are incompatible with MRI

8. Body size that is incompatible with MRI scanner dimensions

9. Anyone already enrolled and actively participating in another greater than minimal risk study.

   PROSPECTIVE SUBJECTS DIAGNOSED WITH STROKE:

10. Other impairments secondary to stroke (e.g., attention, cognition, etc.) that would interfere with the ability to understand study goals or follow simple instructions, as judged by the investigators.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 5 patient groups

Paired, Sub-Threshold Stim

Experimental group

Description:

Sub-threshold stimulation paired with successful task repetitions

Treatment:

Other: Transcutaneous Electrical Stimulation

Paired, Supra-Threshold Stim

Experimental group

Description:

Supra-threshold stimulation paired with successful task repetition

Treatment:

Other: Transcutaneous Electrical Stimulation

Unpaired, Sub-Threshold Stim

Experimental group

Description:

Sub-threshold stimulation after successful task repetition

Treatment:

Other: Transcutaneous Electrical Stimulation

Unpaired, Supra-Threshold Stim

Experimental group

Description:

Supra-threshold stimulation after successful task repetition

Treatment:

Other: Transcutaneous Electrical Stimulation

Sham

Sham Comparator group

Description:

No stimulation

Treatment:

Other: Sham