Infant Feeding Problems, taVNS
Conditions
Brief summary
Feeding is critical for pre-term infants and term infants with hypoxic ischemic brain injury, in order to be discharged home with their families and avoid a gastrostomy tube (G-tube) placement. The proposed study will employ a novel system that stimulates the vagus nerve through the skin in front part of the ear, the BabyStrong feeding system, to delivered transcutaneous auricular vagus nerve stimulation (taVNS) paired with oral feedings daily for 10 days. In an earlier study at Medical University of South Carolina (MUSC), this type of vagus nerve stimulation resulted in more than half of infants who were slated to receive G-tubes, taking full oral feeds by mouth and avoiding a G-tube. In this study some babies will receive the therapy for 10 days and others will get no stimulation. If no progress is made in feeding volumes by day 10, the infants will be switched to the other treatment for 7 days. Parents, study personnel, and care providers will be blinded to taVNS assignment. The electronic stimulation device is Federal Drug Administration (FDA)-cleared for investigational use, and the BabyStrong has been designated a Breakthrough Medical Device by the FDA. This study will be conducted in MUSC's Neonatal Intensive Care Unit.
Detailed description
In this Phase I study, we will conduct a small-scale safety and feasibility study of 2 different taVNS units and ear electrode positions to optimize the BabyStrong portable taVNS feeding system and test the study design of randomization for 10 days. We will test the BabyStrong feeding system using up to n=10 active and n=10 sham taVNS in infants with twice daily treatment for 10 days, with cross over to alternate treatment for another 7days if there is no progress with feeds (increase \<4ml/kg/d). G-tube placement will be arranged if infant continues to make no progress. If the infant attains full oral feeds and gains weight, they may be discharged at any time during the treatment protocol. The treatment assignment will be blinded to care providers, study personnel and parents. We will compare the number of participants who attain full oral feeds (= or \> 130ml/kg/d with weight gain). Safety measures will be bradycardia and discomfort. Criteria for success of BabyStrong feeding system: No sustained increase in discomfort scores; No bradycardia; attainment of full oral feeds in 50% of infants.
Interventions
DEVICEtranscutaneous auricular vagus nerve stimulation
Stimulation of the auricular branch of the left vagus nerve paired with oromotor feeding.
Sham stimulation of the left auricular branch of the vagus nerves paired with oral feeding
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
blinded to study treatment assignment to active or sham taVNS. Perceptual threshold (PT) will be determined in both treatment groups.
Intervention model description
If progress in daily oral feeding volumes is \<4ml/kg/d after 10 days with either treatment A or B, we will offer cross-over to the alternate treatment, remaining blinded to treatment assignment.
Eligibility
Sex/Gender
ALL
Age
2 Weeks to 5 Months
Healthy volunteers
No
Inclusion criteria
* Infants born at any gestational age (GA), failing oral feeds after trying to learn feeding for 2 weeks if term, and 4 weeks if preterm * safe to attempt oral feeds every feed without volume limitations by occupational or speech therapists, and * clinical team is considering the need for a G-tube.
Exclusion criteria
* cardiomyopathy * unstable bradycardia * significant respiratory support * infants of poorly controlled diabetic mothers, defined by obstetrical care providers, HgbA1C\>5.6% or ketonuria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bradycardia | 30 minutes during taVNS paired-feed for 10 days | safety : number of participants with episode of Heart rate \< 80beats per minute for 5 seconds, according to the first assigned treatment |
| Discomfort Scores | 30 minutes during taVNS paired-feed up to 17 days | mean number of participants with Neonatal and Infant Pain scale (NIPS) \>3 point increase, indicating worse discomfort according to the first assigned treatment |
| Participants Who Attain Full Oral Feeds | 17 days | taVNS in participants who received tragus stimulation and attained full oral feeds (oral intake = or \>130ml/kg/day with weight gain) according to the first assigned treatment |
Countries
United States
Participant flow
Recruitment details
recruitment in the neonatal intensive care unit MUSC from 8/1/22 to 5/30/24
Pre-assignment details
n=1 participant made rapid advance in feeds during screening studies prior to receiving any assigned treatment; Design includes a cross-over to alternative blinded treatment if feeding volume increase was \<4ml/kg/d \*participants only cross over between Active and Sham treatments within the same location
Participants by arm
| Arm | Count |
|---|---|
| active taVNS unit tragus/ cymba conchae We will deliver taVNS via the taVNS unit with the ear electrode positioned on left tragus or at the cymba conchae with return to the tragus. Pulses are paired with oral feeding, off with rest during 2 feeds a day. Current will be delivered at 0.1milliAmpere (mA) \< perceptual threshold (PT), 500microseconds, 25 Hertz (Hz).
transcutaneous auricular vagus nerve stimulation: Stimulation of the auricular branch of the left vagus nerve paired with oromotor feeding. | 5 |
| sham taVNS unit tragus/cymbae conchae We will deliver inactive /sham taVNS via the taVNS unit with the ear electrode positioned around left cymba conchae/ inner tragus with return to the outer tragus. No pulses are delivered when pressing trigger, paired with oral feeding during 2 feeds a day. No current will be delivered, and assignment will be blinded.
transcutaneous auricular vagus nerve stimulation: Stimulation of the auricular branch of the left vagus nerve paired with oromotor feeding. | 3 |
| Active taVNS unit cymba conchae/mastoid We will deliver taVNS via the taVNS unit on the vagus channel with the ear electrode positioned around left cymba conchae with return to the mastoid. Pulses are paired with oral feeding, off with rest during 2 feeds a day. Current will be delivered at 0.1milliAmpere (mA) \< perceptual threshold (PT), 500microseconds, 25 Hertz (Hz).
transcutaneous auricular vagus nerve stimulation: Stimulation of the auricular branch of the left vagus nerve paired with oromotor feeding. | 2 |
| Sham taVNS unit cymbae conchae/mastoid We will deliver inactive /sham taVNS via the taVNS unit on the vagus channel with the ear electrode positioned around left cymba conchae with return to the mastoid. No pulses are delivered when pressing trigger, paired with oral feeding during 2 feeds a day. No current will be delivered, and assignment will be blinded.
transcutaneous auricular vagus nerve stimulation: Stimulation of the auricular branch of the left vagus nerve paired with oromotor feeding. | 2 |
| active taVNS crossover to sham taVNS We deliver taVNS via the taVNS unit with the ear electrode positioned on left tragus or at the cymba conchae with return to the tragus. Pulses are paired with oral feeding, off with rest during 2 feeds a day. Current will be delivered at 0.1milliAmpere (mA) \< perceptual threshold (PT), 500microseconds, 25 Hertz (Hz). Following 10 days of active stimulation with feeds, if infant is making \< 4ml/kg/day increase in oral feed volume we will cross over to sham taVNS for up to 7 days of twice daily treatment.
transcutaneous auricular vagus nerve stimulation: Stimulation of the auricular branch of the left vagus nerve paired with oromotor feeding. | 2 |
| Sham taVNS cross over to active taVNS We deliver taVNS via the taVNS unit with the ear electrode positioned on left tragus or at the cymba conchae with return to the tragus. No active pulses are paired with oral feeding, for the sham condition during 2 feeds a day. Following 10 days of sham stimulation with feeds, if infant is making \< 4ml/kg/day increase in oral feed volume we will cross over to active taVNS for up to 7 days of twice daily treatment with current will be delivered at 0.1milliAmpere (mA) \< perceptual threshold (PT), 500microseconds, 25 Hertz (Hz).
transcutaneous auricular vagus nerve stimulation: Stimulation of the auricular branch of the left vagus nerve paired with oromotor feeding. | 2 |
| Total | 16 |
Baseline characteristics
| Characteristic | active taVNS unit tragus/ cymba conchae | sham taVNS unit tragus/cymbae conchae | Active taVNS unit cymba conchae/mastoid | Sham taVNS unit cymbae conchae/mastoid | active taVNS crossover to sham taVNS | Sham taVNS cross over to active taVNS | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 41.2 weeks | 44.6 weeks | 42.8 weeks | 43.6 weeks | 48.6 weeks | 41.5 weeks | 43.5 weeks |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 3 | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 0 / 5 | 0 / 3 | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 |
| serious Total, serious adverse events | 0 / 5 | 0 / 3 | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 |
Outcome results
Primary
Bradycardia
safety : number of participants with episode of Heart rate \< 80beats per minute for 5 seconds, according to the first assigned treatment
Time frame: 30 minutes during taVNS paired-feed for 10 days
Population: Crossover arms are exploratory due to the small sample size.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| active taVNS unit tragus/ cymba conchae | Bradycardia | 0 Participants |
| sham taVNS unit tragus/cymbae conchae | Bradycardia | 0 Participants |
| Active taVNS unit cymba conchae/mastoid | Bradycardia | 0 Participants |
| Sham taVNS unit cymbae conchae/mastoid | Bradycardia | 0 Participants |
| active taVNS cross over to sham taVNS | Bradycardia | 0 Participants |
| Sham taVNS cross over to active taVNS | Bradycardia | 0 Participants |
Primary
Discomfort Scores
mean number of participants with Neonatal and Infant Pain scale (NIPS) \>3 point increase, indicating worse discomfort according to the first assigned treatment
Time frame: 30 minutes during taVNS paired-feed up to 17 days
Population: Crossover arms are exploratory due to the small sample size.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| active taVNS unit tragus/ cymba conchae | Discomfort Scores | 1 Participants |
| sham taVNS unit tragus/cymbae conchae | Discomfort Scores | 3 Participants |
| Active taVNS unit cymba conchae/mastoid | Discomfort Scores | 1 Participants |
| Sham taVNS unit cymbae conchae/mastoid | Discomfort Scores | 0 Participants |
| active taVNS cross over to sham taVNS | Discomfort Scores | 0 Participants |
| Sham taVNS cross over to active taVNS | Discomfort Scores | 0 Participants |
Primary
Participants Who Attain Full Oral Feeds
taVNS in participants who received tragus stimulation and attained full oral feeds (oral intake = or \>130ml/kg/day with weight gain) according to the first assigned treatment
Time frame: 17 days
Population: Crossover arms are exploratory due to the small sample size.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| active taVNS unit tragus/ cymba conchae | Participants Who Attain Full Oral Feeds | 4 Participants |
| sham taVNS unit tragus/cymbae conchae | Participants Who Attain Full Oral Feeds | 2 Participants |
| Active taVNS unit cymba conchae/mastoid | Participants Who Attain Full Oral Feeds | 0 Participants |
| Sham taVNS unit cymbae conchae/mastoid | Participants Who Attain Full Oral Feeds | 2 Participants |
| active taVNS cross over to sham taVNS | Participants Who Attain Full Oral Feeds | 0 Participants |
| Sham taVNS cross over to active taVNS | Participants Who Attain Full Oral Feeds | 0 Participants |