Neonatal Abstinence Syndrome, Neonatal Opioid Withdrawal Syndrome
Conditions
Keywords
auricular neurostimulation, vagus nerve stimulation, transcutaneous, withdrawal symptoms
Brief summary
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
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: 1. Group 1: Active tAN + Morphine 2. 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. After the participant exits the inpatient treatment phase of the study, they will enter the neurodevelopmental follow-up phase. The participant's parent or legal guardian will be contacted at 3, 9, 18, and 24 months of age to complete the Ages and Stages Questionnaire (ASQ-3) and the Sensory Profile 2 (SP-2). At 24 months, participants who fail in any sub-domain will be referred to their primary care physician for further neurodevelopmental assessment using the Bayley Scale of Infant and Toddler Development III (BSID-III) or other neurodevelopmental assessment.
Interventions
DEVICESparrow Fledging Therapy System
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.
DEVICESham Sparrow Fledging Therapy System
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.
Sponsors
Spark Biomedical, Inc.
Medical University of South Carolina
University of Texas Southwestern Medical Center
The University of Texas Health Science Center at San Antonio
National Institute on Drug Abuse (NIDA)
National Institutes of Health (NIH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Each clinical site will have NICU nurses that will perform the Finnegan scale and be blind to the subjects' group designation. This will ensure a non-biased assessment of the Finnegan score, and importantly morphine dosing. Information regarding study intervention will be withheld from the blinded NICU nurses. NNNS assessors will also be blinded to information regarding study intervention to prevent biased NNNS scoring. All investigators will be blinded to subject treatment group.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
33 Weeks to 1 Years
Healthy volunteers
No
Inclusion criteria
1. Neonates or infants \>33 weeks gestational age with NOWS who have withdrawal scores requiring morphine replacement therapy 2. Clinically stable without respiratory support (exception for nasal cannula) 3. Congenital syndromes may be included if the infants do not have major, unrepaired anomalies
Exclusion criteria
1. Unstable infants 2. Repeated episodes of autonomic instability (apnea or bradycardia) which are not self-resolving 3. Major unrepaired congenital anomalies impacting respiratory or cardiovascular system 4. Cardiomyopathy 5. Abnormal ear anatomy preventing the device to fit 6. Infants diagnosed with iatrogenic NOWS 7. Infants two weeks of age or older (after birth) 8. Neonates who have received more than 6 methadone doses or 24 hours of methadone dosing 9. Infants who are wards of the state 10. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Day 1 - Day 30 (or day of discharge) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median length of hospital stay due to NOWS | Through inpatient treatment phase completion, an average of one month | Defined as the number of calendar days from first q3h opioid administration through the 48-hour observation period |
| Median length of hospital stay secondary to NOWS | Through inpatient treatment phase completion, an average of one month | Defined as the number of calendar days from date of birth through date of discharge |
| Neonatal Neurobehavioral Scale (NNNS-II) | Baseline, Day 7, Day 15, and Day 30 (or day of discharge) | 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. |
| Mean number of days of oral morphine medication administered | Day 1 - Day 30 (or day of discharge) | — |
| Mean number of days from birth to medical readiness for discharge | From day of birth through discharge, an average of one month | Defined as the date where all of the following criteria are met: age of at least 96 hours, a period of at least 48 hours without receipt of an opioid, at least 24 hours without respiratory support and with 100% oral feeding, at least 24 hours from initiation of maximum caloric density |
Countries
United States
Outcome results
None listed