Neonatal Abstinence Syndrome
Conditions
Brief summary
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
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.
Interventions
DEVICESpark 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.
Sponsors
Medical University of South Carolina
Spark Biomedical, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
33 Weeks to 1 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 12 days | No adverse events of bradycardia (HR \< 80 bpm), worsening of swallowing or feeding, skin irritation, or elevation of Neonatal Infant Pain Scores. |
| Mean Finnegan Scores During Days of tAN Sessions | 12 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Morphine Weaning | 12 days | Defined as the number of days between tAN therapy initiation and morphine discontinuation. A shorter duration of morphine weaning indicates better treatment efficacy. |
| Length of Hospital Stay | From participant birth to hospital discharge, a median of 17 days | Defined as the number of days between birth and discharge. A shorter length of stay indicates better treatment efficacy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Transcutaneous Auricular Neurostimulation tAN therapy was administered for 30 minutes one hour prior to morphine administration, up to four times per day, for up to 12 days (or discontinuation of morphine; whichever came first).
The Spark Roo tAN System was 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. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Active Transcutaneous Auricular Neurostimulation |
|---|---|
| Age, Customized Gestational Age at Enrollment | 38.2 weeks |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
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.
Time frame: 12 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Transcutaneous Auricular Neurostimulation | Mean Finnegan Scores During Days of tAN Sessions | 6.33 score on a scale | Standard Deviation 0.98 |
Primary
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.
Time frame: 12 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Transcutaneous Auricular Neurostimulation | 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. | 7 Participants |
Secondary
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.
Time frame: 12 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Transcutaneous Auricular Neurostimulation | Duration of Morphine Weaning | 6.0 Days |
Secondary
Length of Hospital Stay
Defined as the number of days between birth and discharge. A shorter length of stay indicates better treatment efficacy.
Time frame: From participant birth to hospital discharge, a median of 17 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Transcutaneous Auricular Neurostimulation | Length of Hospital Stay | 17.0 Days |