Restoration of the Gut Microbiome After Cesarean Section

Official title

"Restoration of the Gut Microbiome After Cesarean Section (RestoreGut)" - A Double-blinded Randomized Placebo-controlled Trial

Overview

This study aims to develop a therapy for restoring the gut microbiome in infants born via CS. The Study will conduct a randomized, placebo-controlled feasibility trial to assess the ability of microbiome restoration by FMT and FVT in infants born by cesarean section.

Detailed description

When a child is born vaginally, the passage through the birth canal provides the first and very important bacterial colonization. As the child ages, various environmental exposures, such as dietary changes and the presence of older siblings in the home, facilitate a natural maturation of the child's gut microbiome, providing a vast and continuous stimulation of the child's developing immune system. However, factors such as mode of delivery and intrapartum antibiotics can perturb this natural developmental process and cause long-term microbial derangements. The prevalence of cesarean section (CS) birth has increased globally in recent decades, and with it, antibiotic treatment to prevent perinatal infection. Similar patterns have occurred for the prevalence of chronic childhood disease, particularly asthma, with an estimated 300 million asthmatic cases worldwide.

The hypothesis is that early intervention with mother-to-infant FMT can restore a CS-perturbed microbiome to a normal microbial trajectory. Another hypothesis is that seeding the virome fraction (FVT) will cause the neonate's microbiome to resemble the mother's since the transferred phages are enriched and preserved in the intestinal mucus layer, thereby providing the recipient with selective antimicrobial protection while allowing species resembling the mother's own to establish during subsequent bacterial transmission.

Interventions

• Biological Microbiome restoration - FMT
  Pathogen-free microbiota from maternal stool sample is transferred from mother to infant.
• Biological Microbiome restoration - FVT
  Sterile-filtered and ultracentrifuged FMT, containing only viruses, is transferred from mother to infant.
• Biological Placebo
  Inactive solution buffer
• Other Vaginal birth, untreated control
  No intervention. This group is for secondary outcomes comparisons.

Primary outcome measures

• Microbial compositional differences compared with placebo-treated infants [Time frame: At 1 week of age]

Secondary outcome measures (7)

• Microbial compositional differences compared with placebo-treated infants [Time frame: During the first year of life]
• Microbial compositional resemblance to vaginally-born infants [Time frame: At 1 week of age]
• Microbial compositional resemblance to vaginally-born infants [Time frame: During the first year of life]
• Virome compositional differences compared with placebo-treated infants [Time frame: At 1 week of age]
• Virome compositional differences compared with placebo-treated infants [Time frame: During the first year of life]
• Virome compositional differences compared with vaginally-born infants [Time frame: At 1 week of age]
• Virome compositional differences compared with vaginally-born infants [Time frame: During the first year of life]

Eligibility criteria

Inclusion criteria

• Gestational age < week 38+0 days
• Proficient in spoken/written Danish
• Single pregnancy (no twins or triplets)
• Pre-pregnancy BMI between 18.5 and 35 kg/m2
• No chronic intestinal, endocrine, cardiac, or kidney disorders
• No known gestational complications (gestational diabetes, preeclampsia, gestational hypothyroidism)
• No regular use of prescription medication or any drugs that, in the research team's opinion, may interfere with the study's results.
• Willingness to abstain from giving the child products with probiotics (fermented dairy like yogurt or A38 are allowed).

Exclusion criteria

Maternal:

• Use of antibiotics within one month of stool donation
• Acute gastroenteritis within one month of stool donation
• Use of antibiotics within one month of birth
• Time since last travel abroad relative to data of fecal donation according to the requirements for blood donations ("Regler for tappepauser" - blooddonor.dk)
• Positive test results for pathogens during donor material screening.
• Antibiotic treatment at birth (vaginal births only)
• Spontaneous onset of labor or emergency cesarean section before scheduled cesarean section.

Infant:

• Instances of major birth defects or intrauterine growth retardation (IUGR)
• Infants requiring pediatric support at the time of transplant administration

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Denmark · 2 centers

• Copsac, DBAC — Gentofte Municipality
• Rigshospitalet — Copenhagen

Identifiers

NCT: NCT06264219 · H-24002284

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗