MicroRNA Biomarkers for Neonatal Opioid Withdrawal Syndrome

Sponsor

Milton S. Hershey Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05937594

Collaborator

National Institute on Drug Abuse (NIDA) (NIH)

Enrollment

Location

Arms

62.8

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Infants with neonatal abstinence syndrome (NAS) experience prolonged hospital stays and poor neurodevelopmental outcomes, in-part because of the lack of accurate, individualized, biologic assessments available to manage this increasingly common medical condition. The proposed study will define the molecular mechanisms that regulate the response to opioid withdrawal in the developing brain by focusing on three candidate microRNAs (let-7a, miR-146a, miR-192) that have been shown to respond to opioid exposure in animal models and adults, and are impacted in both my preliminary study of infants with NAS, and my human neural progenitor cell (NPC) design of opioid withdrawal. By determining the mechanism through which microRNAs impact NPC differentiation in opioid withdrawal, and determining whether exosomal salivary microRNA levels predict treatment dose and neurodevelopmental outcomes in infants with NAS, this study will enhance our knowledge of NAS-related biology and identify potential biomarkers that could improve medical care for this important medical condition.

Condition or Disease	Intervention/Treatment	Phase
Neonatal Opioid Withdrawal Syndrome Neonatal Abstinence Syndrome	Genetic: microRNA-146a level Genetic: microRNA-192 level Genetic: let-7a microRNA level	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Understanding the microRNA Response to Opioid Withdrawal and Their Uses as Potential Biomarkers for Neonatal Abstinence Syndrome

Actual Study Start Date :

Jan 15, 2020

Anticipated Primary Completion Date :

Oct 10, 2024

Anticipated Study Completion Date :

Apr 10, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: microRNA-146a level Saliva will be collected from infants who fulfill inclusion/exclusion criteria.	Genetic: microRNA-146a level Saliva will be collected from neonates who fulfill the inclusion/exclusion criteria. Quantitative polymerase chain reaction (qPCR) will be used to measure salivary miRNAs contained within brain-related exosomes.
Experimental: microRNA-192 level Saliva will be collected from infants who fulfill inclusion/exclusion criteria.	Genetic: microRNA-192 level Saliva will be collected from neonates who fulfill the inclusion/exclusion criteria. Quantitative polymerase chain reaction (qPCR) will be used to measure salivary
Experimental: let-7a level Saliva will be collected from infants who fulfill inclusion/exclusion criteria.	Genetic: let-7a microRNA level Saliva will be collected from neonates who fulfill the inclusion/exclusion criteria. Quantitative polymerase chain reaction (qPCR) will be used to measure salivary

Arm

Intervention/Treatment

Experimental: microRNA-146a level

Saliva will be collected from infants who fulfill inclusion/exclusion criteria.

Genetic: microRNA-146a level

Saliva will be collected from neonates who fulfill the inclusion/exclusion criteria. Quantitative polymerase chain reaction (qPCR) will be used to measure salivary miRNAs contained within brain-related exosomes.

Experimental: microRNA-192 level

Saliva will be collected from infants who fulfill inclusion/exclusion criteria.

Genetic: microRNA-192 level

Saliva will be collected from neonates who fulfill the inclusion/exclusion criteria. Quantitative polymerase chain reaction (qPCR) will be used to measure salivary

Experimental: let-7a level

Saliva will be collected from infants who fulfill inclusion/exclusion criteria.

Genetic: let-7a microRNA level

Saliva will be collected from neonates who fulfill the inclusion/exclusion criteria. Quantitative polymerase chain reaction (qPCR) will be used to measure salivary

Outcome Measures

Primary Outcome Measures

Neurodevelopmental outcome scores [6 months of age]
Measured by Ages and Stages Questionnaire-3, score scale 0-60
Maximum concentration of morphine required for withdrawal symptom control [Measured at 24 hours of life]
Measured in mg/kg/ml

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day to 5 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Newborns ≥35weeks gestation with chronic in-utero opioid exposure (>1month of gestation exposure). Maternal exposure will be determined by evaluating the medical records for maternal medication use, maternal urine toxicology and neonatal meconium toxicology results per standard clinical care
Neonates born at Penn State Hershey Medical Center or transferred at <48 hours after birth
Mothers with chronic in-utero opioid use during pregnancy ( ≥1month of gestation)

Exclusion Criteria:

<35 week gestation
Infant required mechanical ventilation or non-invasive mechanical support
Infant exposure to magnesium sulfate
Opioid-exposed neonates who are actively receiving dextrose infusion for persistent neonatal hypoglycemia at the time of enrollment (<48hours after birth).
Infant with major congenital anomalies
Parent or guardian unable to provide consent
Mothers and neonates without history of opioid exposure/dependence