NAC +taVNS in IDM Who Are Poor Oral Feeders

NCT04632069 | Completed Early Phase 1 Results DMC FDA Drug FDA Device

• 2 other identifiers: 103800P20GM109040
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Infant of Diabetic Mother; Oxidative Stress; Vagus Nerve Stimulation; Feeding Disorders

Outcome Measures

Primary Outcomes (1)

• Daily Oral Feeding Volumes : Difference in Mean Increase

  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)

  Day -14 to 0, Day 1 to 18

Secondary Outcomes (1)

• Metabolite Concentrations in Basal Ganglia

  baseline to 4 days

Study Arms (1)

NAC + taVNS

EXPERIMENTAL

NAC will be given via nasogastric tube (n,g.) 100mg/kg loading dose, then 75mg/kg/dose n.g. q 6h, administered 1h before a feed, for a total of 14 days. taVNS will be administered to left ear during active sucking with 2 daily feedings starting after 4 days of NAC, continuing for 10 days.

Combination Product: N acetyl cysteine + vagus nerve stimulation

Interventions

N acetyl cysteine + vagus nerve stimulation COMBINATION_PRODUCT

NAC x 14 days, taVNS x 10 days

Also known as: NAC, Acetadote, taVNS

NAC + taVNS

Eligibility Criteria

• Age: 3 Weeks - 5 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (2)

• Badran BW, Jenkins DD, Cook D, Thompson S, Dancy M, DeVries WH, Mappin G, Summers P, Bikson M, George MS. Transcutaneous Auricular Vagus Nerve Stimulation-Paired Rehabilitation for Oromotor Feeding Problems in Newborns: An Open-Label Pilot Study. Front Hum Neurosci. 2020 Mar 18;14:77. doi: 10.3389/fnhum.2020.00077. eCollection 2020.

  PMID: 32256328 BACKGROUND

• Badran BW, Jenkins DD, DeVries WH, Dancy M, Summers PM, Mappin GM, Bernstein H, Bikson M, Coker-Bolt P, George MS. Transcutaneous auricular vagus nerve stimulation (taVNS) for improving oromotor function in newborns. Brain Stimul. 2018 Sep-Oct;11(5):1198-1200. doi: 10.1016/j.brs.2018.06.009. Epub 2018 Jun 30. No abstract available.

  PMID: 30146041 BACKGROUND

MeSH Terms

Conditions

Feeding and Eating Disorders

Interventions

Acetylcysteine; Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Electric Stimulation Therapy; Therapeutics

Limitations and Caveats

small numbers in phase I trial; non concurrent control group

Results Point of Contact

• Title: Dr Dorothea Jenkins
• Organization: Medical University of South Carolina

jenkd@musc.edu

843-792-2112

Study Officials

• Dorothea Jenkins, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Co-investigator analyzing MRI data will be blinded to timing of MRI scan and dose
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: November 17, 2020
• Study Start: August 12, 2021
• Primary Completion: March 1, 2024
• Study Completion: July 1, 2024
• Last Updated: August 29, 2024
• Results First Posted: August 29, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: after publication of results
• Access Criteria: written request of PI

Locations

US (1)