tAN to Mitigate Withdrawal Behaviors in Neonates

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

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.

Study Overview

• Status: Completed
• Conditions: Neonatal Abstinence Syndrome
• Intervention / Treatment: Device: Spark Biomedical Roo Transcutaneous Auricular Neurostimulation (tAN) System

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Unstable infants or those requiring significant respiratory support.
2. Repeated episodes of autonomic instability (apnea or bradycardia) which are not self-resolving *
3. Infants <33weeks gestation at enrollment.
4. Major unrepaired congenital anomalies
5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Transcutaneous Auricular Neurostimulation; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Spark Biomedical, Inc.
• Collaborators: Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2020
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 30, 2020

Study Registration Dates

• First Submitted: October 8, 2020
• First Submitted That Met QC Criteria: October 8, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Estimate): December 28, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Infant, Newborn, Diseases; Neonatal Abstinence Syndrome
• Other Study ID Numbers: Pro00090960; 1R43DA050360-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan to share participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No