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.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Neonatal Opioid Withdrawal Syndrome; Neonatal Abstinence Syndrome	Device: Sparrow Fledging Therapy System; Device: Sham Sparrow Fledging Therapy System	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• 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
• Official Title: Delivering Transcutaneous Auricular Neurostimulation as an Adjunct Treatment for Neonatal Opioid Withdrawal Syndrome
• Actual Study Start Date: July 26, 2022
• Estimated Primary Completion Date: August 2023
• Estimated Study Completion Date: September 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active tAN + Morphine	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.
Sham Comparator: Sham tAN + Morphine	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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]
2. 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.

Secondary Outcome Measures :

1. Median length of hospital stay due to NOWS [ Time Frame: Through study completion, an average of one month ]
2. Median length of hospital stay secondary to NOWS [ Time Frame: Through study completion, an average of one month ]
3. 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.

Other Outcome Measures:

1. 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.
2. Median length of time to reach oral morphine control dose [ Time Frame: Duration of morphine administration ]
3. Mean total oral morphine delivered [ Time Frame: Duration of morphine administration ]

Eligibility Criteria

• Ages Eligible for Study: 33 Weeks to 1 Year (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

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

Locations

United States, South Carolina

Medical University of South Carolina - Shawn Jenkins Children's Hospital; Recruiting

Charleston, South Carolina, United States, 29425

Contact: Jessica Morris, RN morrjess@musc.edu

Contact: Kate Bonham bonhamk@musc.edu

Principal Investigator: Dorothea Jenkins, MD

United States, Texas

UT Southwestern Medical Center / Parkland Memorial Hospital; Recruiting

Dallas, Texas, United States, 75235

Contact: Kathryn Mazioniene, RN kathryn.mazioniene@utsouthwestern.edu

Principal Investigator: Lorraine Bautista, MD

Principal Investigator: Venkat Kakkilaya, MD

Sponsors and Collaborators

Spark Biomedical, Inc.

Medical University of South Carolina

University of Texas Southwestern Medical Center

  Study Documents (Full-Text)

Documents provided by Spark Biomedical, Inc.:

Informed Consent Form  [PDF] May 18, 2022

More Information

• Responsible Party: Spark Biomedical, Inc.
• ClinicalTrials.gov Identifier: NCT05129020
• Other Study ID Numbers: SBM-NOWS-02
• First Posted: November 22, 2021
• Last Update Posted: May 3, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

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

• 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

Keywords provided by Spark Biomedical, Inc.:

auricular neurostimulation; vagus nerve stimulation; transcutaneous; withdrawal symptoms

Additional relevant MeSH terms:

Neonatal Abstinence Syndrome; Syndrome; Substance Withdrawal Syndrome; Disease; Pathologic Processes; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Infant, Newborn, Diseases