Clinical trial NCT06057415: Improving Gastrointestinal Function In High-Risk Newborns By Stimulation Of The Enteric Nervous System
Official title: Improving Gastrointestinal Function In High-Risk Newborns By Stimulation Of The Enteric Nervous System
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Feeding and Eating Disorders
Keywords: preterm infants
high-risk newborns
congenital diaphragmatic hernia
autonomous nervous system
tactile stimulation
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Nutricia Research
First posted: 2023-09-28
Enrollment: 200
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The randomization will occur web-based, and will be protected from selection bias by using concealed, stratified and blocked randomization.

The group of preterm infants will randomly be assigned to 2 treatment groups according to 6 strata.

* Gestational age 24+0 - 26+0 weeks + Appropriate for gestational age (AGA)
* Gestational age 24+0 - 26+0 weeks + Small for gestational age (SGA)
* Gestational age 26+1 - 28+0 weeks + AGA
* Gestational age 26+1 - 28+0 weeks + SGA
* Gestational age 28+1 - 29+6 weeks + AGA
* Gestational age 28+1 - 29+6 weeks + SGA
Primary purpose: TREATMENT

Brief summary: The goal of this therapeutical intervention trial is to investigate whether tactile-kinesthaetic and oral sensorimotor stimulation can improve gastrointestional function in preterm infants born before gestational age of 30 weeks and newborns with congenital diaphragmatic hernia. The main question it aims to answer is:

• To determine whether HAPTOS- intervention (Handling Adapted to Postnatal age with Tactile-kinaesthetic and Oral sensorimotor Stimulation) in the particpants results in earlier attainment (postnatal days) of full enteral feeding and/or full oral feeding (post menstrual age) compared to standard care. Researchers will compare an intervention group receiving standard of care plus HAPTOS intervention to a group of patients receiving only current standard of care.

Detailed description: Infants born preterm or with congenital diaphragmatic hernia (CDH) are at risk for several long-term unfavourable outcomes that can be related to feeding difficulties from birth onwards. Adverse nutritional outcomes in both patient groups mainly originate from mechanical dysfunction, based on dysmotility. Mechanical function includes suck-swallow coordination, gastrointestinal sphincter tone, gastric emptying and intestinal motility and is regulated by the complex interplay of the autonomic (ANS) and enteric (ENS) nervous system with modulation by the central nervous system (CNS). The intra-uterine environment provides the fetus with developmentally timed sensory exposures through 'touch' that are necessary for development of sensory control and autonomous coordination of bodily functions. Preterm infants miss out this normal maturation, while newborns with CDH may exhibit a delayed maturation probably as a result of the deviant anatomical situation and the severe illness during the direct postnatal period. In the postnatal situation both patient groups may be confronted with either 'negative' sensory stimulation through exposures such as procedural touch/handling, pain or otherwise a reduction in sensory exposures through avoidance of positive touch in relation to supposed clinical instability. All together this may affect normal development and may lead to sensory deprivation and delayed maturation of the nervous regulation and cerebral maturation. Tactile-kinaesthetic and oral sensorimotor stimulation using positive gentle touch have been shown to positively affect cardiorespiratory stability, weight gain, gastro-intestinal performance, and length of stay in hospital for preterm infants. However, these strategies have not been evaluated in high-risk infants. The current study aims at evaluating an intervention programme that provides positive stimuli through touch adapted to the stage of development of the infant with regard to timing, duration and intensity that supports the maturational development of gastrointestinal functionality. (Handling Adapted to Postnatal age with Tactile-kinaesthetic and Oral sensorimotor Stimulation; HAPTOS intervention). We hypothesize that the HAPTOS intervention will improve the postnatal maturation of the autonomous and enteral nervous system and cause improvements in gastrointestinal motility, enteral and oral feeding and cardiorespiratory stability.

Eligibility criteria: Inclusion Criteria:

1. Preterm birth at gestational age \< 30 weeks or
2. Diagnosis of Congenital Diaphragmatic Hernia
3. Born at Amalia Children's Hospital or admitted 1rst day of life
4. Written informed consent of both parents or representatives

Exclusion Criteria:

1. Preterm infant born at gestational age ≥ 30 weeks
2. Perinatal Asphyxia; (Apgar score at 5' \< 5 and first pH ≤ 7,0)
3. Major congenital anomalies or birth defects other than congenital diaphragmatic hernia;
4. Metabolic disease that necessitates a special diet other than human milk or formula feeding and or has a prognosis of impaired neurological development
5. Parental refusal of participation

Primary outcomes:
measure: Number of days to achieve full enteral feeding
timeFrame: 60 days
measure: Postmenstrual age at achievement of full oral feeding
timeFrame: 52 weeks
Secondary outcomes:
measure: First meconium passage
timeFrame: 14 days
measure: Duration of meconium passage
timeFrame: 14 days
measure: Use of laxatives
timeFrame: 60 days
measure: Gastrointestinal Motility
timeFrame: 100 days
measure: Vomiting
timeFrame: duration of hospitalization up to 15 months
measure: Periodic breathing
timeFrame: duration of hospitalization up to 15 months
measure: Feeding difficulties
timeFrame: 24 months
measure: Maturation of heart rate variability
timeFrame: duration of intensive care stay up to 60 days
measure: Growth at postmenstrual age
timeFrame: at 40 weeks, 3, 6, 12, 18 and 24 weeks
measure: Morbidity
timeFrame: 100 days
measure: Duration hospital stay
timeFrame: 100 days
measure: Neurocognitive development
timeFrame: at 24 months
measure: Parent participation in care
timeFrame: duration of hospitalization up to 100 days
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
Study officials:
affiliation: Radboud University Medical Center
name: Viola Christmann, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: