taVNS Paired With Bottle Feeding in Infants Failing Oral Feeds
Condition: Poor Feeding; Infant Development; Vagus Nerve Stimulation
Study type: Interventional
Phase: Early Phase 1

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.
    

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.
    

Intervention name(s): transcutaneous auricular vagus nerve stimulation
Intervention type(s): Device
Intervention description(s): Microcurrent stimulation delivered to the left tragus, with stimulation 'on' during sucking from a bottle, and 'off' at rest during bottle feeding
Other intervention name(s): taVNS
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: 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.
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment