Understanding the microRNA Response to Opioid Withdrawal and Their Uses as Potential Biomarkers for Neonatal Abstinence Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Neurodevelopmental outcome scores
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Day 至 5 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •<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
研究组 & 干预措施
Infants exposed to in utero opiates
Infants that meet IRB-approved inclusion/exclusion criteria.
干预措施: Buccal swab saliva for further genetic testing (Genetic)
结局指标
主要结局
Neurodevelopmental outcome scores
时间窗: 6 months of age
Measured by Ages and Stages Questionnaire-3, score scale 0-60
Maximum concentration of morphine required for withdrawal symptom control
时间窗: Measured during the course of hospital stay
Measured in mg/kg/ml
Salivary level of microRNA-146a
时间窗: Buccal swab collected within 96 hrs of life and at discharge
Relative fluorescence (Cq) measured by qPCR using established housekeeping gene
Salivary level of microRNA-192
时间窗: Buccal swab collected within 96 hrs of life and at discharge
Relative fluorescence (Cq) measured by qPCR using established housekeeping gene
Salivary level of microRNA-149-3p
时间窗: Buccal swab collected within 96 hrs of life and at discharge
Relative fluorescence (Cq) measured by qPCR using established housekeeping gene
Salivary microRNA level let-7a
时间窗: Buccal swab collected within 96 hrs of life and at discharge
Relative fluorescence (Cq) measured by qPCR using established housekeeping gene
次要结局
未报告次要终点
研究者
Steven Hicks
Associate Professor of Pediatrics
Penn State University