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

NCT06396689 | Not Yet Recruiting

• 1 other identifier: 123
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 2

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.

Conditions

Sleep Problem; Neurobehavioral Manifestations

Keywords

microbiome; infant; gut; metagenomics; development; metabolics; pre-term; probiotics; synbiotics; brain-gut

Outcome Measures

Primary Outcomes (7)

• Sleep-wake behavior

  Brief Infant Sleep Questionnaire BISQ, actinometry and sleep-wake diary

  up to two years of age

• Neuronal connectivity

  High-density EEG during sleep

  up to two years of age

• Neurobehavioral development

  Bayley Scales of Infant Development

  up to two years of age

• Behavior

  Infant Behavior Questionnaire

  up to two years of age

• Gut microbiota

  Composition of stool microbiota

  up to two years of age

• Stool metabolome

  Composition of stool metabolites

  up to two years of age

• Breath metabolome

  Composition of breath metabolites

  up to two years of age

Secondary Outcomes (6)

• Eczema

  up to two years of age

• Food allergy

  up to two years of age

• Rates of infection

  up to two years of age

• Breast milk microbiota

  up to two years of age

• Nasal microbiota

  up to two years of age

Study Arms (4)

Preterm-born infants assigned to "synbiotics" (PRET-SYN)

ACTIVE COMPARATOR

Dietary Supplement: Synbiotic

Preterm-born infants to "placebo" (PRET-PLC)

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Term-born infants to "synbiotics" (TERM-SYN)

ACTIVE COMPARATOR

Dietary Supplement: Synbiotic

Term-born infants to "placebo" (TERM-PLC)

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

Synbiotic DIETARY_SUPPLEMENT

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

Preterm-born infants assigned to "synbiotics" (PRET-SYN); Term-born infants to "synbiotics" (TERM-SYN)

Placebo DIETARY_SUPPLEMENT

The capsule contains zinc oxide, coating agent, methyl hydroxypropyl cellulose, anti-caking agent and magnesium stearat

Preterm-born infants to "placebo" (PRET-PLC); Term-born infants to "placebo" (TERM-PLC)

Eligibility Criteria

• Age: 0 Days - 7 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Preterm-arm:
• neonates born between a gestational age of 34 0/7 to 36 6/7 weeks
• Term-arm
• neonates born at a gestational age of ≥ 37 0/7 weeks Infants need to be

You may not qualify if:

• 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

Sponsors & Collaborators

• Petra Zimmermann: lead
• University of Luzern: collaborator
• Swiss Federal Institute of Technology in Zurich (ETHZ): collaborator

Study Sites (2)

Hopital cantonal Fribourg

Fribourg, Canton of Fribourg, 1700, Switzerland

Location

Cantonal Hospital

Lucerne, Canton of Lucerne, 6000, Switzerland

Location

Related Publications (1)

• Zimmermann P, Kurth S, Giannoukos S, Stocker M, Bokulich NA. NapBiome trial: Targeting gut microbiota to improve sleep rhythm and developmental and behavioural outcomes in early childhood in a birth cohort in Switzerland - a study protocol. BMJ Open. 2025 Mar 3;15(3):e092938. doi: 10.1136/bmjopen-2024-092938.

  PMID: 40032396 DERIVED

MeSH Terms

Conditions

Parasomnias; Neurobehavioral Manifestations; Premature Birth

Interventions

Synbiotics

Condition Hierarchy (Ancestors)

Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Prebiotics; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Probiotics; Food and Beverages

Central Study Contacts

Petra Zimmermann, MD, PhD

CONTACT

+412063060000; petra.zimmermann@unifr.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Head of Paediatrics, Head of Paediatric Infectious Diseases

Study Record Dates

• First Submitted: April 10, 2024
• First Posted: May 2, 2024
• Study Start: March 1, 2025
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): February 28, 2029
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2)