Ignite Creation Date:
2024-05-06 @ 3:27 PM
Last Modification Date:
2024-10-26 @ 1:49 PM
Study NCT ID:
NCT04632069
Status:
COMPLETED
Last Update Posted:
2024-01-11
First Post:
2020-11-12
Brief Title:
NAC taVNS in IDM Who Are Poor Oral Feeders
Sponsor:
Medical University of South Carolina
Organization:
Medical University of South Carolina
Study Overview
Official Title:
N-acetylcysteine Plus Transcutaneous Vagus Nerve Stimulation in Infants of Diabetic Mothers Who Fail Oral Feeding
Status:
COMPLETED
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
Detailed 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 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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P20GM109040 | NIH | None | httpsreporternihgovquickSearchP20GM109040 |