tAN to Mitigate Withdrawal Behaviors in Neonates

Study Overview
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Brief Summary
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This first in-human-neonates, open-label pilot trial is designed to determine whether use of tAN in newborns with NOWS receiving oral morphine allows for faster weaning of morphine and decrease morphine use altogether. Reducing Neonatal Opioid Withdrawal Syndrome (NOWS) symptoms may also help lessen or eliminate the need for opioid medication and shorten the length of the hospital stay. The neurostimulation device, currently called the Roo is a safe form of neurostimulation that uses sticker-like patches worn in and around the ear during the withdrawal period. The patches deliver a small and painless current of electrical pulses to the skin and underlying cranial nerves.

Detailed Description
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This first in-human-neonates, open-label pilot trial is designed to determine whether use of tAN in newborns with NOWS receiving oral morphine allows for faster weaning of morphine and decrease morphine use altogether. After obtaining parental consent, tAN is delivered to the left ear in NOWS newborns who are on a stable morphine dose for >12h (control dose), using a disposable, multi-channel (Channel1: auricular branch of the vagus nerve (ABVN); Channel2: ATN) earpiece electrode (Spark Biomedical, Inc). 30-minutes of tAN is delivered one hour prior to scheduled morphine dose, up to four times daily for up to 12 days. The device is programmed to a pulse width of 250ms; channel 1: 5 Hz, mean intensity 0.3±0.2 milliamps (mA); channel 2: 100 Hz, mean intensity 0.6±0.2 mA. Nurses score the Finnegan Neonatal Abstinence Scoring Tool (FNAST) every 3h after feeding and morphine is weaned every 12h if FNAST scores <8.

Official Title
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Transcutaneous Auricular Neurostimulation (tAN) to Mitigate Withdrawal Behaviors in Neonates With Opioid Withdrawal

Conditions
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Neonatal Abstinence Syndrome

Intervention / Treatment
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* Device: Spark Biomedical Roo Transcutaneous Auricular Neurostimulation (tAN) System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonates or infants with opioid withdrawal or Neonatal Abstinence Syndrome (NAS) who have withdrawal scores requiring morphine replacement therapy. They must be clinically stable, on minimal respiratory support (Continuous positive airway pressure (CPAP), nasal cannula, or room air), >33 weeks gestational age at enrollment, and currently receiving replacement therapy for opioid dependence. Stable neonates who are dependent on opioids, such as after extracorporeal membrane oxygenation, severe illness or brain injury, will be included in this study, as these neonates represent a population in which tAN could minimize withdrawal while not adding to burden of pharmacotherapies. Congenital syndromes may be included if the infants do not have major, unrepaired anomalies. Exclusion Criteria: Unstable infants or those requiring significant respiratory support. Repeated episodes of autonomic instability (apnea or bradycardia) which are not self-resolving * Infants <33weeks gestation at enrollment. Major unrepaired congenital anomalies Cardiomyopathy *Preterm infants commonly have short periods of shallow or absent breathing or lower heart rate termed apnea and bradycardia, respectively, and most are being treated for these physiologic manifestations of prematurity with caffeine, an effective central stimulant. Infants are on cardiorespiratory monitors through the nursery stay with recording devices to capture events and play them back. However, nearly all of these events are self resolving, meaning the infant resolves the breathing pause or bradycardia on their own. Infants who require repeated episodes of stimulation to come out of these events are defined as unstable. Similarly, infants on significant respiratory support are not stable, and will not be eligible.

Ages Eligible for Study
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Minimum Age: 33 Weeks
Maximum Age: 1 Year

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Transcutaneous Auricular Neurostimulation<br>Transcutaneous Auricular Neurostimulation programmed to a pulse width of 250ms; channel 1: 5 Hz, mean intensity 0.3±0.2 mA; channel 2: 100 Hz, mean intensity 0.6±0.2 mA | Device: Spark Biomedical Roo Transcutaneous Auricular Neurostimulation (tAN) System<br>* Spark Roo tAN System programmed to a pulse width of 250ms; channel 1: 5 Hz, mean intensity 0.3±0.2 mA; channel 2: 100 Hz, mean intensity 0.6±0.2 mA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With no Adverse Events Related to Bradycardia (HR < 80 Bpm), Worsening of Swallowing or Feeding, Skin Irritation, or Elevation of Neonatal Infant Pain Scores. | No adverse events of bradycardia (HR < 80 bpm), worsening of swallowing or feeding, skin irritation, or elevation of Neonatal Infant Pain Scores. | 12 days | 
| Mean Finnegan Scores During Days of tAN Sessions | The Finnegan Scale assesses 31 of the most common signs of neonatal drug withdrawal syndrome and is scored on the basis of pathological significance and severity of the adverse symptoms. Scores for each sign are added to obtain a total score. Total scores range from 0-20, where lower scores are indicative of less severe signs of neonatal drug withdrawal symptoms. | 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Morphine Weaning | Defined as the number of days between tAN therapy initiation and morphine discontinuation. A shorter duration of morphine weaning indicates better treatment efficacy. | 12 days | 
| Length of Hospital Stay | Defined as the number of days between birth and discharge. A shorter length of stay indicates better treatment efficacy. | From participant birth to hospital discharge, a median of 17 days |