N-acetylcysteine Plus Transcutaneous Vagus Nerve Stimulation in Infants of Diabetic Mothers Who Fail Oral Feeding
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Daily Oral Feeding Volumes : Difference in Mean Increase
研究概览
简要总结
Infants of diabetic mothers who are failing to learn oral feeding by term age equivalence have greater CNS oxidative stress, which interact to predict poor neuroplasticity response to transcutaneous vagus nerve stimulation paired with oral feeding. We propose treating the oxidative stress in IDM infants prior to initiating taVNS, with an FDA-approved antioxidant (N-acetylcysteine, NAC) to improve CNS oxidative stress, which in turn regulates expression of many genes including BDNF, that may enhance motor learning.
详细描述
Our group has recently conducted a first-in-infants pilot trial of pairing transcutaneous auricular vagus nerve stimulation (taVNS) with feeding to assist learning oromotor skills. We are enrolling preterm and HIE infants who are failing to learn oral feeds and clinically determined to need a G-tube. In preliminary data, taVNS paired with one or two daily feedings for 2 weeks resulted in 50% of infants attaining full feeds and avoiding G-tube.
A notable number of non-responders were infants of diabetic mothers (IDM) exposed to poor glucose control during pregnancy, all of whom required a G-tube. Uncontrolled maternal hyperglycemia is associated with increased systemic and neuro-inflammation, CNS oxidative stress, DNA damage, and worse neonatal outcomes compared to infants of euglycemic mothers. In neonatal animal models, hyperglycemia has been shown to decrease BDNF, alter long-term synaptogenesis and hippocampal neurochemistry, with ongoing CNS oxidative stress and inhibition of the cortical neuronal plasticity required for learning. In our pilot trial of taVNS-paired feeding, CNS glutathione concentrations (GSH), a MR spectroscopy (MRS) marker of oxidative stress, had significant interaction with IDM in predicting outcome, strongly suggesting that ongoing CNS oxidative stress contributes to neuropathology in IDMs failing oral feeding.
NAC is an FDA-approved antioxidant that is safe and crosses the blood brain barrier, increasing CNS GSH. NAC reduces CNS oxidative stress, enhances learning and provides a neuroprotective effect after brain injury in our and others neonatal HI and neuroinflammatory animal models. Both GSH and BDNF enhance neuroplasticity. Therefore, we hypothesize that pre-treatment with NAC in IDMs who are failing oral feeding, followed by taVNS-paired feeding, will decrease oxidative stress induced by maternal hyperglycemia and IDM-associated brain injury, and increase response to taVNS-paired feeding rehabilitation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Co-investigator analyzing MRI data will be blinded to timing of MRI scan and dose
入排标准
- 年龄范围
- 3 Weeks 至 5 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants of diabetic mothers who are failing oral feeding, >39weeks gestation at enrollment, who are clinically stable, on minimal respiratory support (nasal cannula or room air), and clinical team has determined are G-tube candidates
排除标准
- •Unstable infants or those requiring positive pressure respiratory support
- •Infants <39 weeks gestation at enrollment
- •Major unrepaired congenital anomalies or anomalies that limit feeding volumes
- •Infants with cardiomyopathy
- •Repeated episodes of autonomic instability (apnea/ bradycardia) not self resolving
结局指标
主要结局
Daily Oral Feeding Volumes : Difference in Mean Increase
时间窗: Day -14 to 0, Day 1 to 18
Difference in the Mean daily change in oral feeding volume(reported in in ml/kg/d) from Day 1-18 days of NAC+taVNS treatment minus Days -14 to 0 (baseline)
次要结局
- Metabolite Concentrations in Basal Ganglia(baseline to 4 days)
研究者
Dorothea D. Jenkins
Professor of Pediatrics
Medical University of South Carolina