Clinical trial NCT06396689: NapBiome: Targeting Gut Microbiota and Sleep Rhythm to Improve Developmental and Behavioral Outcomes in Early Childhood
Official title: NapBiome: Targeting Gut Microbiota and Sleep Rhythm to Improve Developmental and Behavioral Outcomes in Early Childhood
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Sleep Problem
Neurobehavioral Manifestations
Keywords: microbiome
infant
gut
metagenomics
development
metabolics
pre-term
probiotics
synbiotics
brain-gut
Lead sponsor: University of Fribourg
Sponsor class: OTHER
Collaborators: name: University of Luzern
name: Swiss Federal Institute of Technology in Zurich (ETHZ)
First posted: 2024-05-02
Enrollment: 380
Sex: ALL
Minimum age (years): 0
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: The gut-brain axis plays a crucial role in the regulation and development of psychological and physical processes. The first year of life is a critical period for the development of the gut microbiome, which parallels important milestones in establishing sleep rhythm and neurodevelopment. Growing evidence suggests that the gut microbiome influences sleep, cognition, and early neurodevelopment. For term and preterm-born infants, difficulties in sleep regulation can have major consequences on infants' health, attachment between infants and their caregivers, and can even lead to life-threatening consequences such as shaken-baby syndrome. Preterm born infants are at even higher risk for sleep and neurodevelopmental problems. Although neonatal care has improved over recent decades, preterm birth rates continue to rise and lead to a wide range of neurodevelopmental disabilities that are unaddressed with current therapies. Given the importance of sleep and the gut microbiome for brain maturation, neurodevelopment, and behavior, identifying effective interventions within the gut-brain axis at the beginning of life is likely to have long-term implications for health and development of at-risk infants.

The aims of this project are to I) demonstrate the association between the gut microbiome, sleep patterns and health outcomes in children up to two years of age; and II) to leverage gut microbiome-brain-sleep interactions to develop new intervention strategies for at-risk infants. The investigators hypothesize that the establishment of a healthy gut microbiome during early life is crucial for both short- and long-term child health outcomes, as dysbiosis can harm sleep regulation, brain maturation, and neurobehavioral development. The investigators predict that the administration of synbiotics improves microbiota establishment, sleep rhythm, and neurodevelopmental outcomes.

This project integrates a randomized controlled trial (RCT), ex vivo, and in silico experiments with I) key technology platforms for computational modeling to capture the ontogenic norms of gut microbiota; II) neuronal and actimetry-based quantification of multidimensional aspects of infant sleep; III) breath metabolomics (exhalomics) of host and microbiome metabolism; and IV) high-throughput ex vivo models for investigating host-microbiome interactions. Outcomes include I) an understanding of age-normative microbiome composition, its variation (circadian, inter-individual), and the factors that influence the microbiome's plasticity throughout infancy; II) actionable knowledge of microbial species and metabolism that can be targeted to modify sleep regulation and improve neurodevelopmental outcomes, especially in at-risk infants (e.g., preterm-born); III) microbial and metabolic biomarkers with diagnostic potential for later regulatory and behavioral problems; and IV) an open-source analytical "toolbox" for microbial multi-omics that can be immediately applied in other areas of microbiome-host research. To achieve these goals, our strategy combines multiple disciplines focusing on factors that exert the greatest influence on health during infancy: the gut microbiome, sleep regulation, and neurodevelopment.

The impact of this project is substantial and globally relevant, as it advances possible treatment options for supporting neurodevelopmental health in preterm- and term-born infants, explores novel translational approaches for addressing regulatory difficulties, and provides key information for tailored prophylactic synbiotics and possible development of "post-biotics". Further, the study supports the investigation of biomarkers for neurodevelopment and advances early prevention of developmental and mental illnesses.


Eligibility criteria: Inclusion Criteria:

Preterm-arm:

* neonates born between a gestational age of 34 0/7 to 36 6/7 weeks
* partially breast-fed at the time of inclusion

Term-arm

* neonates born at a gestational age of ≥ 37 0/7 weeks Infants need to be
* partially breast-fed at the time of inclusion

Exclusion Criteria:

Infants who

* receive probiotics outside the trial design
* have a birth weight \< 1500 g
* were prenatally drug-exposed (cannabis, cocaine, heroin, opiates, and alcohol)
* have suspected or confirmed immunodeficiency
* have an underlying disease (excluding transient conditions such as alimentation problems, hyperbilirubinemia, hypoglycaemia, anemia, respiratory distress syndrome or apnea-bradycardia syndrome), congenital malformations, central nervous system disease or injury or congenital infections

Primary outcomes:
measure: Sleep-wake behavior
timeFrame: up to two years of age
measure: Neuronal connectivity
timeFrame: up to two years of age
measure: Neurobehavioral development
timeFrame: up to two years of age
measure: Behavior
timeFrame: up to two years of age
measure: Gut microbiota
timeFrame: up to two years of age
measure: Stool metabolome
timeFrame: up to two years of age
measure: Breath metabolome
timeFrame: up to two years of age
Secondary outcomes:
measure: Eczema
timeFrame: up to two years of age
measure: Food allergy
timeFrame: up to two years of age
measure: Rates of infection
timeFrame: up to two years of age
measure: Breast milk microbiota
timeFrame: up to two years of age
measure: Nasal microbiota
timeFrame: up to two years of age
measure: Oral microbiota
timeFrame: up to two years of age
Other outcomes:
Locations:
city: Fribourg
country: Switzerland
facility: Hopital cantonal Fribourg
city: Lucerne
country: Switzerland
facility: Cantonal Hospital
Study officials:
References: