Restoration of the Gut Microbiome After Cesarean Section

Microbial Colonization Clinical Trial

— RestoreGut  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06264219
• Other study ID #: H-24002284
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: March 1, 2024
• Est. completion date: November 30, 2026

Study information

• Verified date: February 2024
• Source: Copenhagen Studies on Asthma in Childhood
• Contact: Jakob Stokholm, MD, PhD
• Phone: +45 38677360
• Email: stokholm[@]copsac.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to develop a therapy for restoring the gut microbiome in infants born via CS. We 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.

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. We hypothesize that early intervention with mother-to-infant FMT can restore a CS-perturbed microbiome to a normal microbial trajectory. We also hypothesize 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: November 30, 2026
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Microbial Colonization

Intervention

Biological:
• Microbiome restoration - FMT
Pathogen-free microbiota from maternal stool sample is transferred from mother to infant.
• Microbiome restoration - FVT
Sterile-filtered and ultracentrifuged FMT, containing only viruses, is transferred from mother to infant.
• Placebo
Inactive solution buffer

Other:
• Vaginal birth, untreated control
No intervention. This group is for secondary outcomes comparisons.

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen
Denmark	Copsac, DBAC	Gentofte	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Professor Klaus Bønnelykke

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microbial development trajectory	Compositional differences to placebo-treated infants	During the first year of life
Secondary	Microbial development trajectory	Compositional resemblance to vaginally-born infants	During the first year of life