Neurostimulation to Improve NOWS Outcomes

Study Overview
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Brief Summary
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The objective of this study is to determine if tAN therapy can reduce the median number of days of oral morphine administered to an infant after start of treatment.

Detailed Description
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This study is designed as a randomized, double-blind, sham-controlled, multi-center, clinical trial in which neonates diagnosed with Neonatal Opioid Withdrawal Syndrome (NOWS) will be randomized 1:1 into one of two treatment groups: Group 1: Active tAN + Morphine Group 2: Sham tAN + Morphine Morphine dosing for all infants will be managed by using the Finnegan Neonatal Abstinence Scoring System (FNASS), recorded every three hours.

Official Title
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Delivering Transcutaneous Auricular Neurostimulation as an Adjunct Treatment for Neonatal Opioid Withdrawal Syndrome

Conditions
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Neonatal Opioid Withdrawal Syndrome, Neonatal Abstinence Syndrome

Intervention / Treatment
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* Device: Sparrow Fledging Therapy System
* Device: Sham Sparrow Fledging Therapy System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Neonates or infants >33 weeks gestational age with NOWS who have withdrawal scores requiring morphine replacement therapy Clinically stable or on minimal respiratory support (continuous positive airway pressure [CPAP], nasal cannula, or room air) Stable neonates who are dependent on opioids following 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 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 Major unrepaired congenital anomalies impacting respiratory or cardiovascular system Cardiomyopathy Abnormal ear anatomy preventing the device to fit Infants diagnosed with iatrogenic NOWS without intrauterine exposure Infants two weeks of age or older (after birth) Neonates who have received more than 6 methadone doses or 24 hours of methadone dosing Infants who are wards of the state Participant has any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is designed as a randomized, double-blind, sham-controlled, multi-center, clinical trial in which neonates diagnosed with Neonatal Opioid Withdrawal Syndrome (NOWS) will be randomized 1:1 into one of two treatment groups.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active tAN + Morphine<br> | Device: Sparrow Fledging Therapy System<br>* tAN sessions will be administered up to four times per day for up to 20 days total. Active tAN will be set to run for 30 minutes one hour prior to each planned morphine dose. When the 30-minute tAN session is complete, the system will be turned off and unplugged.<br>|
| Sham Comparator: Sham tAN + Morphine<br> | Device: Sham Sparrow Fledging Therapy System<br>* Participants randomized to the sham group will have the device earpiece applied at the same timepoints and for the same duration as the active group, but stimulation will not be turned on. tAN sessions will be administered up to four times per day for up to 20 days total. Sham tAN will be set to run for 30 minutes one hour prior to each planned morphine dose. When the 30-minute tAN session is complete, the system will be turned off and unplugged.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median number of days of oral morphine medication administered to the infant after start of active or sham tAN treatment. |  | Duration of morphine administration | 
| Finnegan Neonatal Abstinence Scoring System (FNASS) | Finnegan Neonatal Abstinence Scoring System (FNASS) is a validated assessment tool designed to measure 21 signs of withdrawal in infants. The tool provides a means to rate severity of withdrawal symptoms every three hours after feeding using a standard format. | Day 1 - Day 30 (or day of discharge) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median length of hospital stay due to NOWS |  | Through study completion, an average of one month | 
| Median length of hospital stay secondary to NOWS |  | Through study completion, an average of one month | 
| Neonatal Neurobehavioral Scale (NNNS-II) | The NNNS is a comprehensive and systematic assessment of an infant's response to a variety of items including handling, spontaneous behavior, motor activity and self-soothing as indicators of neurobehavioral performance. The NNNS examines neurobehavioral organization, neurological reflexes, motor development, active and passive tone, and signs of stress and withdrawal of the at-risk and drug-exposed infant. The NNNS document the range of withdrawal and stress behavior likely to be observed in intervention with substance-exposed infants. The scale consists of 13 domains: habituation, attention, arousal, regulation, handling procedures, quality of movement, excitability, lethargy, nonoptimal reflexes, asymmetric reflexes, hypertonicity, hypotonicity, and stress/abstinence scale. Summary scores are calculated and compared with percentile scores to determine how an infant compares with an at-risk sample. The NNNS has good psychometric properties and reliability. | Baseline, Day 7, Day 15, and Day 30 (or day of discharge) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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auricular neurostimulation, vagus nerve stimulation, transcutaneous, withdrawal symptoms