Restoration of the Gut Microbiome After Cesarean Section

NCT ID: NCT06264219

Last Updated: 2024-09-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-02
• Study Completion Date: 2026-11-30

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.

Conditions

Microbial Colonization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

FMT (Fecal microbiota transplantation)

Mother-to-infant fecal microbiota transplantation

Group Type: ACTIVE_COMPARATOR

Microbiome restoration - FMT

Intervention Type: BIOLOGICAL

Pathogen-free microbiota from maternal stool sample is transferred from mother to infant.

FVT (Fecal virome transplantation)

Mother-to-infant fecal virome transplantation

Group Type: ACTIVE_COMPARATOR

Microbiome restoration - FVT

Intervention Type: BIOLOGICAL

Sterile-filtered and ultracentrifuged FMT, containing only viruses, is transferred from mother to infant.

Placebo

Inactive solution buffer placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Inactive solution buffer

Vaginal control group

Non-randomized control group used for secondary outcomes comparisons.

Group Type: OTHER

Vaginal birth, untreated control

Intervention Type: OTHER

No intervention. This group is for secondary outcomes comparisons.

Interventions

Microbiome restoration - FMT

Pathogen-free microbiota from maternal stool sample is transferred from mother to infant.

Intervention Type: BIOLOGICAL

Microbiome restoration - FVT

Sterile-filtered and ultracentrifuged FMT, containing only viruses, is transferred from mother to infant.

Intervention Type: BIOLOGICAL

Placebo

Inactive solution buffer

Intervention Type: BIOLOGICAL

Vaginal birth, untreated control

No intervention. This group is for secondary outcomes comparisons.

Intervention Type: OTHER

Other Intervention Names

Fecal Microbiota Transplantation; Fecal Virome Transplantation

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Professor Klaus Bønnelykke

OTHER

Sponsor Role: lead

Responsible Party

Professor Klaus Bønnelykke

Professor PhD, Head of COPSAC

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Klaus Bønnelykke, MD, PhD

Role: STUDY_CHAIR

Head of COPSAC

Locations

Copsac, DBAC

Gentofte Municipality, Copenhagen, Denmark

Site Status: RECRUITING

Rigshospitalet

Copenhagen, , Denmark

Site Status: NOT_YET_RECRUITING

Countries

Denmark

Central Contacts

Jakob Stokholm, MD, PhD

Role: CONTACT

stokholm@copsac.com

+45 38677360

Kaare D. Tranæs, Msc

Role: CONTACT

kaare.tranaes@dbac.dk

+45 38677360

Facility Contacts

Jakob Stokholm, MD, PhD

Role: primary

stokholm@copsac.com

+45 38677360

Hanne Hegaard, Professor

Role: primary

Hanne.Kristine.Hegaard@regionh.dk

+45 27583632

Other Identifiers

H-24002284

Identifier Type: -

Identifier Source: org_study_id