Extending taVNS Paired With Infant CIMT Into a Home-Based Setting

Study Overview
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Brief Summary
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Newborns who are born premature or suffer brain injury at birth are at risk for motor problems that may cause weakness in reaching and grasping on one side of the body. In older children, therapists may use a hand mitt and restraint for the stronger arm, to encourage use of the weaker side, called constraint-induced movement therapy (CIMT). Even with the high intensity therapy of CIMT, it typically takes between 40-120 hours total treatment time for most children to improve their motor skills. A non-invasive form of nerve stimulation, transcutaneous auricular vagus nerve stimulation (taVNS), stimulates a nerve by the ear that enhances learning motor skills. taVNS stimulation will be triggered by EMG sensors which detect muscle activity. The purpose of this study is to evaluate the safety and effectiveness of taVNS to improve motor skills when paired with CIMT in infants with one-sided weakness at 6-18 months of age.

Detailed Description
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Preterm birth and complications in term births can result in increased risk for intraventricular hemorrhage, global hypoxia-ischemia (HIE), arterial stoke, and neuroinflammation with white matter injury in newborns. CNS injuries then may manifest as early developmental delays and motor weakness in the first 12 months, that presage hemiplegic cerebral palsy (CP). Early targeted therapy interventions for high-risk infants aim to improve neurological outcomes by taking advantage of critical windows for neuroplasticity. Intensive interventions, such as constraint-induced movement therapy (CIMT), are designed to ameliorate early motor predecessors of CP in at-risk infants. This intervention must be provided at a minimally effective dosage of 40 hours, and 60-120 hours for optimal outcomes, and are typically provided in a condensed time period, over 4 to 6 weeks with intensive task-practice for 3-6 hours a day. Delivering CIMT within the context a typical family day is a challenge. Interventional strategies that reduce the time requirement while offering the same or better outcomes would benefit families and facilitate treatment delivery. Few studies have used neuromodulation combined with intensive motor therapies, such as CIMT, to enhance neuroplasticity and improve functional outcomes in children. Transcranial direct current stimulation has been used safely in older children with CP during bimanual learning therapy. Our group is the first to use non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) paired with a motor task of bottle-feeding in infants with feeding failure. taVNS paired with motor feeding activity was safe and over 50% infants determined to need a gastrostomy tube (G-tube) attained full oral feeds (mean time to full oral feeds 15 days with once daily, and 7.8 days with twice daily treatment). This study will use EMG sensing of muscle activity to trigger the taVNS system. Use of EMG sensors is hypothesized to improve pairing of stimulation with motor activity while also decreasing the treatment burden for the therapist.

Official Title
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Extending taVNS Paired With Infant CIMT Into a Home-Based Setting: Technology Development Requisite for a Randomized Trial

Conditions
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Cerebral Palsy

Intervention / Treatment
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* Combination Product: Custom EMG triggered Soterix taVNS stimulation with CIMT therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Five 6-18-month-old infants Hemiplegia/motor asymmetry qualifying for Constraint Induced Movement Therapy Gross Motor Function Classification System (GMFCS) level I-IV Ability to maintain a sitting position for 5 minutes with moderate assistance Exclusion Criteria: GMFCS level V Severe motor impairment/ quadriplegic involvement Uncorrected blindness or deafness Cardiomyopathy

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: For this study we are making modifications to the taVNS stimulation (Soterix unit) system. These modifications include using Electromyography (EMG) muscle sensors to trigger stimulation instead of a manual button. We are also transitioning the manual stimulation option to Bluetooth to improve ease of use in the clinic with infants. The taVNS stimulation will be paired with constraint induced movement therapy (CIMt) an established rehabilitation intervention. The Soterix taVNS unit is FDA registered and is a custom version of an FDA cleared device.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Soterix taVNS stimulation using EMG sensors<br>We will trial use of a new taVNS unit that uses automated EMG sensors to trigger stimulation and an optional Bluetooth manual trigger. This experimental device will be used to during CIMT rehabilitation treatment to pair stimulation with active movement. | Combination Product: Custom EMG triggered Soterix taVNS stimulation with CIMT therapy<br>* Participants will receive taVNS stimulation paired with 40 hours of constraint-induced movement therapy. The new device will automatically trigger stimulation using EMG muscle sensors worn during the therapy session.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Feasibility | Feasibility is measured as percent of total treatment time EMG can successfully trigger stimulation during a CIMT rehabilitation session. | end of 4 week treatment intervention (40 hours of CIMT) | 
| Treatment fidelity | Fidelity Rating of Quality of Constraint Induced Movement Therapy Delivery while using the experimental EMG triggered Soterix taVNS stimulator. | end of 4 week treatment intervention (40 hours of CIMT) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in motor function | Assessment of change in functional motor outcomes pre and post intervention on the Quality of Upper Extremity Skills Test (QUEST) | Change in functional motor outcome completed pre and post 40 hours of treatment |