taVNS Paired With Bottle Feeding in Infants Failing Oral Feeds

NCT04643808 | Completed Early Phase 1 Results DMC FDA Device

• 3 other identifiers: 67997P20GM109040P2CHD086844
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Oromotor dysfunction and poor feeding is common after premature birth and hypoxic ischemic encephalopathy (HIE). Pairing vagus nerve stimulation (VNS) with motor activity accelerates functional improvements after stroke. This study is designed to investigate whether transcutaneous auricular VNS (taVNS) paired with oromotor rehabilitation is tolerable, safe, and facilitates motor learning in infants who have failed oral feeding.

Conditions

Poor Feeding; Infant Development; Vagus Nerve Stimulation

Outcome Measures

Primary Outcomes (3)

• Number of Infants Who Took All Feeds by Mouth (Responders)

  Number of infants who maintained full daily PO intake for 4 days (\>120 ml/kg/day) and gained weight adequate for discharge (\>20 g/day) were classified as 'Responders'.

  3 weeks

• ml/kg/d Increase Over 7d During taVNS

  The change in ml/kg/d of oral feeds over the 7 days during taVNS-paired feeds

  7 days

• Neuroplasticity as Measured by the Change in White Matter Tract Integrity Via Fractional Anisotropy

  changes in radial kurtosis diffusion in Corticospinal tracts at the cerebellar peduncles assessed per week of treatment, change from baseline to week 3 reported. Kurtosis is a dimensionless summary statistic that quantifies the amount of non-Gaussianity within the tissue on a scale from 0 to infinity. Higher values indicate greater complexity in the white matter tract. The scale has no title other than diffusion kurtosis.

  change from baseline to week 3

Secondary Outcomes (2)

• Number of Episodes of Bradycardia

  3 weeks, during taVNS sessions

• Number of Treatment Sessions With Sustained Increase in 'Neonatal and Infant Pain Scale' (NIPS) Scores During taVNS

  30min treatment session

Study Arms (2)

taVNS once daily

EXPERIMENTAL

taVNS paired with bottle feeding once daily for 2-3 weeks

Device: transcutaneous auricular vagus nerve stimulation

taVNS twice daily

EXPERIMENTAL

taVNS paired with bottle feeding twice daily for 2-3 weeks

Device: transcutaneous auricular vagus nerve stimulation

Interventions

transcutaneous auricular vagus nerve stimulation DEVICE

Microcurrent stimulation delivered to the left tragus, with stimulation 'on' during sucking from a bottle, and 'off' at rest during bottle feeding

Also known as: taVNS

taVNS once daily; taVNS twice daily

Eligibility Criteria

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

You may qualify if:

• Infants must be clinically stable, on minimal respiratory support (nasal cannula, or room air), are not restricted for attempting every feed by mouth, and are currently failing oral feeding such that the clinical team is broaching gastrostomy tube (G-tube) placement with the parents. The infant will be greater than or equal to 39weeks gestation at enrollment and either
• Premature at birth and attempting oral feeds for at least 3 weeks or
• Infants who are neart-term or term at birth, with significant medical issues that have precluded oral feeding, such as hypoxic ischemic encephalopathy (HIE), and attempting oral feeds for at least 2 weeks.

You may not qualify if:

• Unstable infants or those requiring positive pressure respiratory support.
• Infants \<38weeks gestation at enrollment.
• Major unrepaired congenital anomalies or anomalies that limit feeding volumes
• Cardiomyopathy
• Repeated episodes of autonomic instability (apnea or bradycardia) which are not self resolving

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute of General Medical Sciences (NIGMS): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (4)

• 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 RESULT

• 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 RESULT

• Cook DN, Thompson S, Stomberg-Firestein S, Bikson M, George MS, Jenkins DD, Badran BW. Design and validation of a closed-loop, motor-activated auricular vagus nerve stimulation (MAAVNS) system for neurorehabilitation. Brain Stimul. 2020 May-Jun;13(3):800-803. doi: 10.1016/j.brs.2020.02.028. Epub 2020 Feb 27.

  PMID: 32289710 RESULT

• Jenkins DD, Moss HG, Adams LE, Hunt S, Dancy M, Huffman SM, Cook D, Jensen JH, Summers P, Thompson S, George MS, Badran BW. Higher Dose Noninvasive Transcutaneous Auricular Vagus Nerve Stimulation Increases Feeding Volumes and White Matter Microstructural Complexity in Open-Label Study of Infants Slated for Gastrostomy Tube. J Pediatr. 2023 Nov;262:113563. doi: 10.1016/j.jpeds.2023.113563. Epub 2023 Jun 16.

  PMID: 37329979 DERIVED

Limitations and Caveats

no concurrent control group, open label dose study (not randomized)

Results Point of Contact

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

jenkd@musc.edu

843-792-2112

Study Officials

• Dorothea Jenkins, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• Bashar Badran, PhD

  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: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Co-investigators analyzing diffusion MRI data were blinded to the timing of the MRI scans (pre- and post-treatment) and dose of taVNS.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: The study investigators delivered taVNS once or twice a day during a bottle feed for 2 weeks. Stimulation was paired with nutritive sucking and swallowing, and was paused during rest or burping. If PO feeds had not progressed after 2 weeks of taVNS treatment, the parents and the clinical team made decisions about timing of G-tube placement. If substantial progress in po feeds was made during the treatment period, but the infant was not quite to full oral feeds, the clinical team and parents could elect to continue for 1-2 weeks.

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: November 25, 2020
• Study Start: October 1, 2017
• Primary Completion: June 1, 2022
• Study Completion: July 1, 2022
• Last Updated: October 30, 2023
• Results First Posted: October 30, 2023

Record last verified: 2023-10

Locations

US (1)