NapBiome: Targeting Gut Microbiota and Sleep Rhythm to Improve Developmental and Behavioral Outcomes in Early Childhood

Neurobehavioral Manifestations Clinical Trial

— NapBiome  

Official title:

NapBiome: Targeting Gut Microbiota and Sleep Rhythm to Improve Developmental and Behavioral Outcomes in Early Childhood

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06396689
• Other study ID #: 123
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2024
• Est. completion date: August 31, 2028

Study information

• Verified date: May 2024
• Source: University of Fribourg
• Contact: Petra Zimmermann, MD, PhD
• Phone: +412063060000
• Email: petra.zimmermann[@]unifr.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 380
• Est. completion date: August 31, 2028
• Est. primary completion date: August 31, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Days to 7 Days

Eligibility

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

Related Conditions & MeSH terms

• Dyssomnias
• Neurobehavioral Manifestations
• Parasomnias
• Sleep Problem

Intervention

Dietary Supplement:
• Synbiotic
The capsule contains Lactobacillus helveticus R0052, Bifidobacterium infantis R0033, and Bifidobacterium bifidum R0071 (3 billion bacteria per capsule), as well as zinc oxide, potato starch fructooligosaccharides, coating agent, methyl hydroxypropyl cellulose, anti-caking agent and magnesium stearat
• Placebo
The capsule contains zinc oxide, coating agent, methyl hydroxypropyl cellulose, anti-caking agent and magnesium stearat

Locations

Country	Name	City	State
Switzerland	Hopital cantonal Fribourg	Fribourg
Switzerland	Cantonal Hospital	Lucerne

Sponsors (3)

Lead Sponsor	Collaborator
Petra Zimmermann	ETH Zurich, University of Luzern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sleep-wake behavior	Brief Infant Sleep Questionnaire BISQ and Actinometry	up to two years of age
Primary	Neuronal connectivity	High-density EEG during sleep	up to two years of age
Primary	Neurobehavior development	Bayley Scales of Infant Development and Ages and Stages Questionnaire	up to two years of age
Primary	Behavior	Infant Behavior Questionnaire	up to two years of age
Primary	Gut microbiota	Composition investigated trough shotgun metagenomic sequencing	up to two years of age
Primary	Breath metabolome	Metabolites using secondary electrospray ionization massspectronomy	up to two years of age
Secondary	Eczema	SCORing Atopic Dermatitis scoring system (SCORAD)	up to two years of age
Secondary	Food allergy	Skin prick test	up to two years of age
Secondary	Rates of infection	Number of episodes	up to two years of age
Secondary	Breast milk microbiota	Composition investigated trough shotgun metagenomic sequencing	up to two years of age
Secondary	Nasal microbiota	Composition investigated trough shotgun metagenomic sequencing	up to two years of age
Secondary	Oral microbiota	Composition investigated trough shotgun metagenomic sequencing	up to two years of age