Neurostimulation to Improve NOWS Outcomes (SPROUT)

• ClinicalTrials.gov Identifier: NCT05129020
• Recruitment Status: Recruiting
• First Posted: November 22, 2021
• Last Update Posted: May 3, 2023
• Sponsor: Spark Biomedical, Inc.
• Collaborators: Medical University of South Carolina; University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Spark Biomedical, Inc.

Tracking Information

• First Submitted Date: November 4, 2021
• First Posted Date: November 22, 2021
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: July 26, 2022
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2022)

• Median number of days of oral morphine medication administered to the infant after start of active or sham tAN treatment. [ Time Frame: Duration of morphine administration ]
• Finnegan Neonatal Abstinence Scoring System (FNASS) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: November 19, 2021)

• Median number of days of oral morphine medication administered to the infant after start of active or sham tAN treatment. [ Time Frame: Duration of morphine administration ]
• Proportion of infants who experience one or more treatment-related adverse events. [ Time Frame: Duration of enrollment ]

Current Secondary Outcome Measures (submitted: August 1, 2022)

• Median length of hospital stay due to NOWS [ Time Frame: Through study completion, an average of one month ]
• Median length of hospital stay secondary to NOWS [ Time Frame: Through study completion, an average of one month ]
• Neonatal Neurobehavioral Scale (NNNS) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: November 19, 2021)

• Median length of hospital stay due to NOWS [ Time Frame: Through study completion, an average of one month ]
• Median length of hospital stay secondary to NOWS [ Time Frame: Through study completion, an average of one month ]
• Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) [ Time Frame: 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.
• Eat, Sleep, Console (ESC) [ Time Frame: Day 1 - Day 30 ]
  All infants will undergo ESC assessment every three hours after feeding (in line with FNASS). An infant will be considered well managed if the infant is able to eat >1 oz per feed or breastfeed well, sleep undisturbed >1 hour, and to be consoled, if crying, within 10 minutes. If the infant is eating <1 oz per feed or not breastfeeding well, sleeping <1 hour undisturbed, and/or is not consolable within 10 minutes, the morphine dose (predicted) will be increased by 0.01 mg/kg. Morphine dose (predicted) will be decreased by 0.04 mg per dose daily if the infant is considered well managed by the ESC standards. Due to its recent introduction, the safety and effectiveness of using ESC has yet to be demonstrated. Therefore, we will continue to use the FNASS to guide treatment decisions. However, treatment decisions made using the FNASS will be compared with predicted treatment decisions based on recorded ESC evaluation.
• Finnegan Neonatal Abstinence Scoring System (FNASS) [ Time Frame: 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.
• Neonatal Infant Pain Scale (NIPS) [ Time Frame: Day 1 - Day 30 (or day of discharge) ]
  The Neonatal Infant Pain Scale (NIPS) is a validated pain scale utilized in the NICU. There are six components to the NIPS: facial expression, crying, breathing patterns, arm and leg movements, and state of arousal. The NIPS scale scoring ranges from 0-7, with scores greater than 3 indicating discomfort. A score of 3 is similar to the pain level associated with a heel stick procedure to obtain blood and the maximum score of 6 is similar to a circumcision procedure without analgesia. This measure will be taken immediately prior to, during, and after tAN therapy.

Current Other Pre-specified Outcome Measures (submitted: February 9, 2022)

• Neonatal Infant Pain Scale (NIPS) [ Time Frame: Day 1 - Day 30 (or day of discharge) ]
  The Neonatal Infant Pain Scale (NIPS) is a validated pain scale utilized in the NICU. There are six components to the NIPS: facial expression, crying, breathing patterns, arm and leg movements, and state of arousal. The NIPS scale scoring ranges from 0-7, with scores greater than 3 indicating discomfort. A score of 3 is similar to the pain level associated with a heel stick procedure to obtain blood and the maximum score of 6 is similar to a circumcision procedure without analgesia. This measure will be taken immediately prior to, during, and after tAN therapy.
• Median length of time to reach oral morphine control dose [ Time Frame: Duration of morphine administration ]
• Mean total oral morphine delivered [ Time Frame: Duration of morphine administration ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Neurostimulation to Improve NOWS Outcomes
• Official Title: Delivering Transcutaneous Auricular Neurostimulation as an Adjunct Treatment for Neonatal Opioid Withdrawal Syndrome
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Quadruple (Participant, Care Provider, 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.

Primary Purpose: Treatment

Condition

• Neonatal Opioid Withdrawal Syndrome
• Neonatal Abstinence Syndrome

Intervention

• Device: Sparrow 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.
• Device: Sham 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.

Study Arms

• Experimental: Active tAN + Morphine
  Intervention: Device: Sparrow Fledging Therapy System
• Sham Comparator: Sham tAN + Morphine
  Intervention: Device: Sham Sparrow Fledging Therapy System

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 19, 2021): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2023
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

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 or on minimal respiratory support (continuous positive airway pressure [CPAP], nasal cannula, or room air)
3. 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
4. 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. 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 without intrauterine exposure
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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 33 Weeks to 1 Year (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Caroline Benner; 8179332727; caroline.benner@sparkbiomedical.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05129020
• Other Study ID Numbers: SBM-NOWS-02
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: There is no plan to share participant data.

• Current Responsible Party: Spark Biomedical, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Spark Biomedical, Inc.
• Original Study Sponsor: Same as current

Collaborators

• Medical University of South Carolina
• University of Texas Southwestern Medical Center

• Investigators: Not Provided
• PRS Account: Spark Biomedical, Inc.
• Verification Date: May 2023