Clinical trial NCT05129020: Neurostimulation to Improve NOWS Outcomes
Official title: Delivering Transcutaneous Auricular Neurostimulation as an Adjunct Treatment for Neonatal Opioid Withdrawal Syndrome
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Neonatal Opioid Withdrawal Syndrome
Neonatal Abstinence Syndrome
Keywords: auricular neurostimulation
vagus nerve stimulation
transcutaneous
withdrawal symptoms
Lead sponsor: Spark Biomedical, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Medical University of South Carolina
name: University of Texas Southwestern Medical Center
name: University of Texas Health Science Center San Antonio
First posted: 2021-11-22
Enrollment: 52
Sex: ALL
Minimum age (years): 33
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Median number of days of oral morphine medication administered to the infant after start of active or sham tAN treatment.
timeFrame: Duration of morphine administration
measure: Finnegan Neonatal Abstinence Scoring System (FNASS)
timeFrame: Day 1 - Day 30 (or day of discharge)
Secondary outcomes:
measure: Median length of hospital stay due to NOWS
timeFrame: Through inpatient treatment phase completion, an average of one month
measure: Median length of hospital stay secondary to NOWS
timeFrame: Through inpatient treatment phase completion, an average of one month
measure: Neonatal Neurobehavioral Scale (NNNS-II)
timeFrame: Baseline, Day 7, Day 15, and Day 30 (or day of discharge)
measure: Mean number of days of oral morphine medication administered
timeFrame: Day 1 - Day 30 (or day of discharge)
measure: Mean number of days from birth to medical readiness for discharge
timeFrame: From day of birth through discharge, an average of one month
Other outcomes:
measure: Median length of time to reach oral morphine control dose
timeFrame: Day 1 - Day 30 (or day of discharge)
measure: Mean total oral morphine delivered
timeFrame: Day 1 - Day 30 (or day of discharge)
measure: Proportion of infants with episode(s) of bradycardia
timeFrame: Day 1 - Day 30 (or day of discharge)
measure: Proportion of infants with episode(s) of apnea related to tAN
timeFrame: Day 1 - Day 30 (or day of discharge)
measure: Proportion of infants with episode(s) of laryngospasms related to tAN
timeFrame: Day 1 - Day 30 (or day of discharge)
measure: Neonatal Infant Pain Scale (NIPS)
timeFrame: Day 1 - Day 30 (or day of discharge)
measure: Number of infants with an Ages and Stages Questionnaire-3 (ASQ-3) Score greater than 2 standard deviations below the mean for any domain
timeFrame: At 3, 9, 18, and 24 months of age
measure: Number of infants who have scores outside of "typical performance", as calculated by a score greater than 1 standard deviation away from the mean, on the Sensory Profile 2 (SP-2)
timeFrame: At 3, 9, 18, and 24 months of age
measure: Proportion of participants who do not meet criteria for normal neurodevelopment as measured by the Bayley Scale of Infant and Toddler Development III (BSID-III) or other neurodevelopmental assessment
timeFrame: At 24 months of age
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina - Shawn Jenkins Children's Hospital
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center / Parkland Memorial Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center San Antonio
state: Texas
Study officials:
References: