Clinical trial NCT06264219: Restoration of the Gut Microbiome After Cesarean Section
Official title: "Restoration of the Gut Microbiome After Cesarean Section (RestoreGut)" - a Double-blinded Randomized Controlled Feasibility Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Microbial Colonization
Lead sponsor: Copenhagen Studies on Asthma in Childhood
Sponsor class: OTHER
First posted: 2024-02-16
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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

Primary outcomes:
measure: Microbial compositional differences to placebo-treated infants
timeFrame: During the first year of life
Secondary outcomes:
measure: Microbial compositional resemblance to vaginally-born infants
timeFrame: During the first year of life
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Copsac, DBAC
state: Copenhagen
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: Head of COPSAC
name: Klaus Bønnelykke, MD, PhD
role: STUDY_CHAIR
References: