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NCT Number: NCT06264219

Restoration of the Gut Microbiome After Cesarean Section

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.

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

Copsac, DBAC, Gentofte Municipality, Copenhagen, Denmark

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Microbiome restoration - FMT

Biological

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

Other names: Fecal Microbiota Transplantation

Microbiome restoration - FVT

Biological

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

Other names: Fecal Virome Transplantation

Placebo

Biological

Inactive solution buffer

Vaginal birth, untreated control

Other

No intervention. This group is for secondary outcomes comparisons.

Primary outcomes

  1. Microbial compositional differences compared with placebo-treated infants

    Time frame: At 1 week of age

    Intestinal microbiome composition, assessed by metagenomic sequencing of fecal matter bacterial DNA, quantified by beta-diversity indices.

Secondary outcomes

  1. Microbial compositional differences compared with placebo-treated infants

    Time frame: During the first year of life

    Intestinal microbiome composition, assessed by metagenomic sequencing of fecal matter bacterial DNA, quantified by beta-diversity indices.

  2. Microbial compositional resemblance to vaginally-born infants

    Time frame: At 1 week of age

    Intestinal microbiome composition, assessed by metagenomic sequencing of fecal matter bacterial DNA, quantified by beta-diversity indices.

  3. Microbial compositional resemblance to vaginally-born infants

    Time frame: During the first year of life

    Intestinal microbiome composition, assessed by metagenomic sequencing of fecal matter bacterial DNA, quantified by beta-diversity indices.

  4. Virome compositional differences compared with placebo-treated infants

    Time frame: At 1 week of age

    Intestinal virome composition, assessed by metagenomic sequencing of fecal viral DNA, quantified by beta-diversity indices.

  5. Virome compositional differences compared with placebo-treated infants

    Time frame: During the first year of life

    Intestinal virome composition, assessed by metagenomic sequencing of fecal viral DNA, quantified by beta-diversity indices.

  6. Virome compositional differences compared with vaginally-born infants

    Time frame: At 1 week of age

    Intestinal virome composition, assessed by metagenomic sequencing of fecal viral DNA, quantified by beta-diversity indices.

  7. Virome compositional differences compared with vaginally-born infants

    Time frame: During the first year of life

    Intestinal virome composition, assessed by metagenomic sequencing of fecal viral DNA, quantified by beta-diversity indices.

Other outcomes

  1. Stool metabolite differences compared with placebo-treated infants

    Time frame: At 1 week of age

    Fecal metabolomic profiles, assessed with GC-MS and LC-MS or Nuclear Magnetic Resonance (NMR)

  2. Stool metabolite differences compared with placebo-treated infants

    Time frame: During the first year of life

    Fecal metabolomic profiles, assessed with GC-MS and LC-MS or Nuclear Magnetic Resonance (NMR)

Study contacts

Contact information is provided by the study sponsor or research team.

Jakob Stokholm, MD, PhD

CONTACT

[email protected]

+45 38677360

Kaare D. Tranæs, Msc

CONTACT

[email protected]

+45 38677360

Sponsors and collaborators

Lead sponsor

Jakob Stokholm

Other

Registry information

Official study title

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

Acronym: RestoreGut

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Feb 16, 2024
Registry last updated
Jun 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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