- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04643808
taVNS Paired With Bottle Feeding in Infants Failing Oral Feeds
Noninvasive Brain Stimulation to Improve Oromotor Function In Neonates With Advanced Neuroimaging to Determine Safety and Target Engagement of taVNS for Neurorehabilitation
Study Overview
Status
Intervention / Treatment
Detailed Description
Feeding difficulty is the primary reason for delayed hospital discharge from the neonatal intensive care unit (NICU), with increased hospital costs and a negative impact on neurodevelopment. Occupational or speech therapists typically start oral stimulation programs early, then feed infants by mouth (PO) daily to encourage safe feeding while learning this motor skill. Even after weeks or months of rehabilitation with therapists, many infants need a gastrostomy tube (G-tube) surgically placed for adequate nutrition. With improved survival rates of more critically ill neonates, the national rate of G-tube placement has doubled from 2000-2012.
Difficulty learning the motor sequence for oral feeding may be due to brain injury from infection, ischemia, and dysmaturity. In these infants, the normal integrative connectivity that occurs after birth between the cortex, basal ganglia, and brainstem may be disturbed, resulting in poor coordination and failure to learn the complex motor task of feeding, when it should be a normal reflex. Therapies that facilitate motor learning and enhance feeding skills would have a significant impact for infants who fail feeding rehabilitation.
In neonates with brain dysmaturity or overt brain injury, neuromodulation of abnormal circuits may positively boost neuronal connectivity and enhance neuroplasticity. Vagus nerve stimulation (VNS) paired with motor activity facilitates cortical reorganization and neurogenesis, and improves motor function in animal stroke models. A noninvasive form of VNS, transcutaneous auricular VNS (taVNS), targets the auricular branch of the vagus nerve to activate vagal afferent and efferent networks. In adult patients with limb impairment after brain injury, pairing taVNS with motor activation is safe, enhances plasticity and improves functional motor recovery. This work in adult humans extends and supports the animal evidence that pairing VNS with a motor or behavioral intervention restores brain function.
The study investigators applied the model of taVNS paired with a motor behavior to infants in the NICU in a prospective, open-label trial exploring the use of once and twice daily taVNS-paired rehabilitation training to enhance oral feeding in infants who are failing oral feeds and slated to receive a G-tube.
After obtaining informed consent, MRIs are obtained before starting treatment, and at end of 2-3 week treatment period. In a subset of 10 patients the study investigators also obtain modified barium swallows prior to and after the treatment period, with taVNS on and off during swallowing. Daily feeding volumes as well as the slope of change of po feeding volumes are recorded before and after starting taVNS.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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South Carolina
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Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
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.
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: taVNS once daily
taVNS paired with bottle feeding once daily for 2-3 weeks
|
Microcurrent stimulation delivered to the left tragus, with stimulation 'on' during sucking from a bottle, and 'off' at rest during bottle feeding
Other Names:
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Experimental: taVNS twice daily
taVNS paired with bottle feeding twice daily for 2-3 weeks
|
Microcurrent stimulation delivered to the left tragus, with stimulation 'on' during sucking from a bottle, and 'off' at rest during bottle feeding
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Infants Who Took All Feeds by Mouth (Responders)
Time Frame: 3 weeks
|
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
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ml/kg/d Increase Over 7d During taVNS
Time Frame: 7 days
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The change in ml/kg/d of oral feeds over the 7 days during taVNS-paired feeds
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7 days
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Neuroplasticity as Measured by the Change in White Matter Tract Integrity Via Fractional Anisotropy
Time Frame: change from baseline to week 3
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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
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Episodes of Bradycardia
Time Frame: 3 weeks, during taVNS sessions
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bradycardic episodes = heart rate <80 beats per minute for 5 seconds
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3 weeks, during taVNS sessions
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Number of Treatment Sessions With Sustained Increase in 'Neonatal and Infant Pain Scale' (NIPS) Scores During taVNS
Time Frame: 30min treatment session
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Number of treatment sessions with sustained increase of 3 points in Neonatal and Infant Pain Scale (NIPS) scores from before to during taVNS: NIPS recorded at before, midway, and at the end of each treatment session.
NIPS scores range from 0 (no discomfort) to 7 (maximum discomfort).
An increase of 3 points on the NIPS scale indicates more discomfort with stimulation.
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30min treatment session
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Dorothea Jenkins, MD, Medical University of South Carolina
- Principal Investigator: Bashar Badran, PhD, Medical University of South Carolina
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 67997
- P2CHD086844 (U.S. NIH Grant/Contract)
- P20GM109040 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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