NAC +taVNS in IDM Who Are Poor Oral Feeders
Last updated on July 2021Recruitment
- Recruitment Status
- Not yet recruiting
- Estimated Enrollment
- Same as current
Summary
- Conditions
- Feeding Disorders
- Infant of Diabetic Mother
- Oxidative Stress
- Vagus Nerve Stimulation
- Type
- Interventional
- Phase
- Early Phase 1
- Design
- Allocation: N/AIntervention Model: Single Group AssignmentIntervention Model Description: We will obtain parental consent, and then administer NAC 100mg/kg loading dose, followed by 75mg/kg q 6h via nasogastric tube, started 4 days prior to taVNS-paired feeding and continued for a total of 14 days. We will perform pharmacokinetics of oral NAC, and MRIs prior to, after 3-4 days of NAC, and after taVNS treatment period.Masking: None (Open Label)Masking Description: Co-investigator analyzing MRI data will be blinded to timing of MRI scan and dosePrimary Purpose: Treatment
Participation Requirements
- Age
- Younger than 5 years
- Gender
- Both males and females
Description
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...
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.
Tracking Information
- NCT #
- NCT04632069
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Investigators
- Principal Investigator: Dorothea Jenkins, MD Medical University of South Carolina
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