Somatosensory Modulation of Salivary Gene Expression and Oral Feeding in Preterm Infants

NCT02696343 | Completed Results DMC

• 1 other identifier: UNL IRB Project ID #15446
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 4

Brief Summary

Two innovative approaches, pulsatile orocutaneous entrainment of non-nutritive suck via orosensory entrainment (NTrainer) device technology and serial salivary gene expression analyses, will be merged to examine the relation between gene expression, oral somatosensory stimulation, feeding behavior, and neurodevelopmental outcomes at 18 months corrected age (CA) on 180 extremely preterm infants \[EPIs\] (24 0/7-26 6/7 GA and 27 0/7 - 28 6/7 GA) enrolled at three neonatal intensive care units: Catholic Health Initiative (CHI) Health St. Elizabeth (Lincoln, NE), Tufts Medical Center (Boston, MA), and Santa Clara Valley Medical Center (San Jose, CA). EPIs will be randomized to a blind pacifier (SHAM) or PULSED NTrainer treatment groups, and stratified by GA, sex, and bronchopulmonary dysplasia status (BPD vs non-BPD). We hypothesize that the combination of the NTrainer® intervention for improved oral feeding skills, along with objective salivary gene expression data to monitor response to treatment and feeding development, will result in a novel, objective, and personalized approach to neonatal oral feeding and reduce the duration of time to attain oral feeds while improving feeding, growth and neurodevelopmental outcomes at 18 months' CA.

Conditions

Feeding Behavior; Infant, Extremely Low Birth Weight

Keywords

somatosensory stimulation; orocutaneous; gene expression

Outcome Measures

Primary Outcomes (1)

• Salivary Gene Expression

  RT PCR gene expression profiles for CDH13 (Cadherin 13, a protein Coding gene), FOXP2 (encodes a member of the forkhead/winged-helix (FOX) family of transcription factors), NPHP4 (Nephronophthisis 4), NPY2R (Neuropeptide Y2 receptor), PLXNA1 (involved in several processes, including generation of neurons; regulation of GTPase activity; and regulation of cell shape), and Wingless-type integration site family (WNT3). Data presented here represent the median values and interquartile range, combined across measurement timepoints. All genes were run on the RT-qPCR platform in duplicate. Normalized gene expression was calculated by the delta CT-method.

  Normalized gene expression data were obtained from a single salivary sample collected weekly from 30 wks (baseline) through 34 wks PMA when NTrainer intervention ceased. Phase1 samples collected 31-32 wks PMA; phase2 samples collected 33-34 wks PMA.

Secondary Outcomes (9)

• NNS Bursts/Minute

  Mixed modeling (LMM) repeated measures used to analyze NNS Bursts/min. Means and S.E. reported in the Measure Description were derived from LMM. The Mean represents overall average of the NNS Bursts/min across multiple time points, (adj. GA, PMA, Sex).

• Time-to-transition to Full Oral Feed

  Time expressed in days for an infant to attain full oral feed (100% PO), assessed on a daily basis beginning at 30 weeks PMA through their stay in the NICU, for an average of fifty-six %PO measures sampled over 8 weeks.

• NNS Cycles/Min

  Mixed modeling (LMM) repeated measures used to analyze NNS Cycles/min. Means and S.E. reported in the Measure Description were derived from LMM. The Mean represents overall average of the NNS Cycles/min across multiple time points, (adj. GA, PMA, Sex).

• Non-nutritive Suck Spatiotemporal Index (NNS STI)

  Mixed modeling (LMM) repeated measures used to analyze NNS STI. Means and S.E. reported in the Measure Description were derived from LMM. The Mean represents overall average of the NNS STI across multiple time points, (adj. GA, PMA, Sex).

• Non-nutritive Suck Compression Amplitude (cmH2O)

  Beginning at 30 weeks PMA, we completed repeated sampling and calculation of non-nutritive suck compression amplitude (cm H2O) from a 2-min digitized sample 3 times per week during the infant's stay in the NICU.

Study Arms (2)

EPI experimental

EXPERIMENTAL

Preterm infants randomized to receive the PULSED orocutaneous somatosensory stimulation from the NTrainer during tube feedings.

Device: NTrainer

EPI control

SHAM COMPARATOR

Preterm infants randomized to receive the Sham (blind pacifier) during tube feedings.

Device: SHAM blind pacifier

Interventions

SHAM blind pacifier DEVICE

regular green Soothie pacifier paired with tube feedings

EPI control

NTrainer DEVICE

pulsed orocutaneous stimulation paired with tube feedings

EPI experimental

Eligibility Criteria

• Age: Up to 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Extremely preterm infants (EPIs) born between 24 0/7 and 28 6/7 weeks' GA, as determined by obstetric ultrasound at \< 15 weeks or last menstrual period
• Enroll EPIs once they have a corrected PCA of ≥ 29 weeks

You may not qualify if:

• Chromosomal and congenital anomalies including craniofacial malformation, nervous system anomalies, cyanotic congenital heart disease, gastroschisis, omphalocele, diaphragmatic hernia and/or other major gastrointestinal anomalies
• Congenital infection
• No documented GA
• Severe IUGR (3%)
• Head circumference \< 10th or \> 90th percentile
• Intracranial hemorrhage grades III and IV, seizures
• Meningitis
• Neurological examination showing abnormal tone or movements of all extremities for PCA
• History of necrotizing enterocolitis (stage II and III)
• Culture-positive sepsis at the time of study enrollment

Sponsors & Collaborators

• California Institute for Medical Research: collaborator
• Texas Tech University: collaborator
• Children's Hospital of Orange County: collaborator
• Tufts Medical Center: collaborator
• CIRI/CHI Institute for Research and Innovation: collaborator
• University of Nebraska Lincoln: lead

Study Sites (4)

Children's Hospital of Orange County

Los Angeles, California, 92868-4203, United States

Location

Santa Clara Valley Medical Center

San Jose, California, 95128-2604, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111-1526, United States

Location

CHI St. Elizabeth's Medical Center

Lincoln, Nebraska, 68512, United States

Location

Related Publications (1)

• Barlow SM, Maron JL, Alterovitz G, Song D, Wilson BJ, Jegatheesan P, Govindaswami B, Lee J, Rosner AO. Somatosensory Modulation of Salivary Gene Expression and Oral Feeding in Preterm Infants: Randomized Controlled Trial. JMIR Res Protoc. 2017 Jun 14;6(6):e113. doi: 10.2196/resprot.7712.

  PMID: 28615158 DERIVED

MeSH Terms

Conditions

Feeding Behavior

Condition Hierarchy (Ancestors)

Behavior, Animal; Behavior

Limitations and Caveats

Participant enrollment at Tufts Med Center \[Boston, MA\], Santa Clara Valley Med Center (San Jose, CA), and Children's Hospital Orange County (Orange, CA) was interrupted in YR2020 and YR2021 due to COVID-19.

Results Point of Contact

• Title: Dr. Steven M. Barlow
• Organization: University of Nebraska-Lincoln

steven.barlow@unl.edu

402-472-2145

Study Officials

• Steven M Barlow, PhD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

• Jill L Maron, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2016
• First Posted: March 2, 2016
• Study Start: July 13, 2016
• Primary Completion: May 9, 2021
• Study Completion: March 31, 2023
• Last Updated: February 27, 2026
• Results First Posted: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

US (4)