BabyStrong Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) Paired Bottle Feeding to Improve Oral Feeding

Study Overview
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Brief Summary
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Feeding is critical for pre-term infants and term infants with hypoxic ischemic brain injury, in order to be discharged home with their families and avoid a gastrostomy tube (G-tube) placement. The proposed study will employ a novel system that stimulates the vagus nerve through the skin in front part of the ear, the BabyStrong feeding system, to delivered transcutaneous auricular vagus nerve stimulation (taVNS) paired with oral feedings daily for 10 days. In an earlier study at Medical University of South Carolina (MUSC), this type of vagus nerve stimulation resulted in more than half of infants who were slated to receive G-tubes, taking full oral feeds by mouth and avoiding a G-tube. In this study some babies will receive the therapy for 10 days and others will get no stimulation. If no progress is made in feeding volumes by day 10, the infants will be switched to the other treatment for 7 days. Parents, study personnel, and care providers will be blinded to taVNS assignment. The electronic stimulation device is Federal Drug Administration (FDA)-cleared for investigational use, and the BabyStrong has been designated a Breakthrough Medical Device by the FDA. This study will be conducted in MUSC's Neonatal Intensive Care Unit.

Detailed Description
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In this Phase I study, we will conduct a small-scale safety and efficacy study of the BabyStrong portable taVNS feeding system. We will test the BabyStrong feeding system using active (n=10) and sham (n=10) taVNS in infants with twice daily (A or B treatment) for 10 days, with cross over to B/A treatment if there is no progress with feeds within 10 days of taVNS treatment. Subsequent A /B treatment will be continued for another 7 days for any treatment effect, prior to arranging for G-tube placement if infant continues to make no progress. If the infant attains full oral feeds and gains weight, they may be discharged at any time during the treatment protocol. The treatment assignment will be blinded to care providers, study personnel and parents. We will compare daily oral feeding volumes over 10 days prior and the 10 days of treatment, and diffusion magnetic resonance imaging (MRI) changes before and after 10 days of taVNS treatment, and after another 7days if the cross-over design is employed. Safety measures will be bradycardia and discomfort, as in our prior taVNS feeding pilot trial, taVNs paired with bottle feeding in infants failing oral feeds National Clinical Trials #04643808. Criteria for success of BabyStrong feeding system: No sustained increase in discomfort scores; No bradycardia; Improvement in daily feeding volumes compared with pre-taVNS, and/or attainment of full oral feeds in 50% of infants; improvement in white matter microstructure by diffusion MRI before and after active treatment.

Official Title
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BabyStrong taVNS-Paired Bottle Feeding to Improve Oral Feeding

Conditions
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Infant Feeding Problems, taVNS

Intervention / Treatment
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* Device: transcutaneous auricular vagus nerve stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants born at any gestational age (GA), failing oral feeds after trying to learn feeding for 2 weeks if term, and 4 weeks if preterm safe to attempt oral feeds every feed without volume limitations by occupational or speech therapists, and clinical team has determined will likely need a G-tube. Exclusion Criteria: cardiomyopathy unstable bradycardia significant respiratory support infants of poorly controlled diabetic mothers, defined by obstetrical care providers, HgbA1C>5.6% or ketonuria.

Ages Eligible for Study
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Minimum Age: 2 Weeks
Maximum Age: 5 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: If progress in daily oral feeding volumes is <4ml/kg/d (based on response rate in pilot trial) after 10 days with either treatment A or B, we will offer cross-over to the alternate treatment.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: active taVNS<br>We will deliver taVNS via the BabyStrong system, with pulses paired with oral feeding, off with rest during 2 feeds a day. Current will be delivered at 0.1milliAmpere (mA) < perceptual threshold (PT), 500microseconds, 25 Hertz (Hz).The ear electrode will be positioned on left tragus for active taVNS. | Device: transcutaneous auricular vagus nerve stimulation<br>* Stimulation of the auricular branch of the left vagus nerve paired with oromotor feeding.<br>* Other names: taVNS, transcutaneous VNS;|
| Sham Comparator: sham taVNS<br>The ear electrode positioned on left tragus as for active taVNS. We will test the PT with active stimulation, and then program a sham setting on the BabyStrong unit to deliver no current after the PT is determined. | Device: transcutaneous auricular vagus nerve stimulation<br>* Stimulation of the auricular branch of the left vagus nerve paired with oromotor feeding.<br>* Other names: taVNS, transcutaneous VNS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bradycardia | safety : episodes of Heart rate < 80beats per minute for 10 seconds | 30 minutes during taVNS paired-feed | 
| discomfort scores | Neonatal and Infant Pain scale (NIPS) >3 point increase | 30 minutes during taVNS paired-feed | 
| increase in oral feeding volumes | slopes of daily po volumes over the first 10 days of treatment; compare between sham and active taVNS | 20 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| white matter tract neuroplasticity | change in fractional anisotropy by diffusion imaging before and after active vs sham treatment | 10 days |