Preterm Infant Intestinal Microbiota Development and Maternal Fecal Transplant

NCT ID: NCT06227845

Last Updated: 2024-02-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-29

Study Completion Date

2026-12-31

Brief Summary

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The goal of this clinical trial is to study if a oral maternal fecal transplant given to a premature infant born by cesarean section (CS) is safe. The investigators will also compare the gut microbiome of the infants to those born by CS and not received the transplant and to premature infants born vaginally.

Detailed Description

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At the Department of Obstetrics at Helsinki University Hospital the investigators will recruit 36 pregnant women (allowing for screening positivity) between 29 and 34 weeks of pregnancy with for example pre-eclampsia or cervix insufficiency, but are otherwise healthy. The mothers fecal sample is carefully screened in case of contagious diseases. The investigators are aiming to recruit 18 mothers with negative screening samples.

The infants are born at gestational week 30-35 either vaginally or by CS. Group A (study group): 10 preterm infants born by CS. These infants will receive a maternal FMT, which will be administered when they tolerate milk at least 40 mL/day. Group B (comparison group): 8 preterm infants from the screening negative mothers and 4 infants from the mothers who have a positive finding in the screening samples (in case the positive finding is a mild pathogen e.g. Dientamoeba fragilis or Blastocystis hominis) born by CS. In case of antibiotic treatment of the infant, the transplant is given not earlier than 48 hours after the last dose, but not later than 7 days of age. Group C: Comparison group of preterm infants born vaginally 30-35 weeks of gestation. For the comparison group, only fecal samples are obtained as in the other groups.

For group A, blood samples are taken on the day of transplant and 1 and 3 days after. The samples are the same as in SECFLOR main trial: research samples and assessment of routine inflammatory markers (such as CBC and CRP).

From the comparison group (B) CRP and blood count samples are taken as ordered by the treating physician. To assess immunological markers a sample of 1 mL is taken at the age of 5-7 days concomitantly with blood samples ordered by the treating physician. No additional samples are taken from the vaginal delivery group.

From all groups: Meconium sample is collected, and then a stool sample on the day of the transplant, and two days after (from the intervention group only) and starting from 1 weeks of age weekly until the age of 4 weeks or until discharged from the intensive unit. After discharge the parents will collect a stool sample of the child at the age of 3, 6, 9 and 12 months.

Blood samples 1-3mL from all infants born by CS (group A and B) are taken at the age of three and six months to assess immunodevelopment.

Methods Fecal samples: The mothers are asked to provide a fresh stool sample at 29-34 weeks. This is processed for DNA isolation and stored in saline and glycerol. A home sampling stool kit is provided for sampling the mothers and infant's feces from diapers. The intestinal microbiota of mothers and infants is determined using 16S rRNA based analysis using next generation sequencing. Fecal DNA is extracted by repeated bead beating and processed for sequencing using pre-defined primers. DNA extractions and MiSeq runs include internal reference samples and a mock community. Metagenomic analysis will be conducted essentially. Resistance genes will be characterized by mapping metagenomic reads nucleotide to nucleotide against the CARD and Resfinder databases to search for acquired antibiotic resistance genes (ARGs).

Blood samples: The development of all major immune cell populations is analyzed by mass cytometry and 267 plasma proteins by immunoassays. About 100 ul whole blood is collected for mass cytometry analysis and mixed with Cytodelics Whole Blood Cell Stabilizer at a ratio of 1:1, incubated in room temperature for 10 minutes and transferred to a 80C freezer for long-term storage awaiting analysis. Plasma samples are obtained, PBMCs are isolated using density gradient-based separation.

Conditions

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Microbial Colonization

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Intervention

10 infants born by CS to screening negative mothers receive an oral maternal fecal transplant (from their own mother) containing 0.35mg/kg of maternal fecal content at the age of 2-7 days of age.

Group Type EXPERIMENTAL

Fecal microbiota transplant

Intervention Type OTHER

0.1-0.3 ml liquid containing 3.5 mg/ml of maternal fecal content, (0.35mg/kg)

Control

12 infants born by CS (8 to screening negative mothers and 4 to screening positive mothers in case of Blastocystis hominis or Dientamoeba fragilis).

Group Type NO_INTERVENTION

No interventions assigned to this group

Comparison

Infants born vaginally to mothers with screening negative or mild pathogene findings (Blastocystis hominis or Dientamoeba fragilis)

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Fecal microbiota transplant

0.1-0.3 ml liquid containing 3.5 mg/ml of maternal fecal content, (0.35mg/kg)

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Pregnant women with preeclampsia or other risk factors of preterm labor (eg cervix insufficiency or placenta previa) between 29+0 - 34+0 weeks of pregnancy.
* Either parent fluent in Finnish.

Exclusion Criteria

* Women with other significant medical conditions including acute infection, IBD, celiac disease.
* Travelling outside the EU and use of antibiotics during the last 3 months.
* Gestational diabetes with insulin medication.
* Pregnant with multiples.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Karolinska Institutet

OTHER

Sponsor Role collaborator

University of Helsinki

OTHER

Sponsor Role collaborator

Otto Helve

OTHER

Sponsor Role lead

Responsible Party

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Otto Helve

Docent

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Otto Helve, Docent

Role: PRINCIPAL_INVESTIGATOR

University of Helsinki

Locations

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Helsinki University Hospital

Helsinki, Uusimaa, Finland

Site Status

Countries

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Finland

Central Contacts

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Noora K Carpén, MD

Role: CONTACT

+358 9 4711

Samuli Rautava, Associate Professor

Role: CONTACT

+358 9 4711

Facility Contacts

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Noora Carpén

Role: primary

Samuli Rautava, As. prof

Role: backup

References

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Carpen N, Brodin P, de Vos WM, Salonen A, Kolho KL, Andersson S, Helve O. Transplantation of maternal intestinal flora to the newborn after elective cesarean section (SECFLOR): study protocol for a double blinded randomized controlled trial. BMC Pediatr. 2022 Sep 29;22(1):565. doi: 10.1186/s12887-022-03609-3.

Reference Type BACKGROUND
PMID: 36175995 (View on PubMed)

Korpela K, de Vos WM. Early life colonization of the human gut: microbes matter everywhere. Curr Opin Microbiol. 2018 Aug;44:70-78. doi: 10.1016/j.mib.2018.06.003. Epub 2018 Aug 4.

Reference Type BACKGROUND
PMID: 30086431 (View on PubMed)

Van Belkum M, Mendoza Alvarez L, Neu J. Preterm neonatal immunology at the intestinal interface. Cell Mol Life Sci. 2020 Apr;77(7):1209-1227. doi: 10.1007/s00018-019-03316-w. Epub 2019 Oct 1.

Reference Type BACKGROUND
PMID: 31576423 (View on PubMed)

Olin A, Henckel E, Chen Y, Lakshmikanth T, Pou C, Mikes J, Gustafsson A, Bernhardsson AK, Zhang C, Bohlin K, Brodin P. Stereotypic Immune System Development in Newborn Children. Cell. 2018 Aug 23;174(5):1277-1292.e14. doi: 10.1016/j.cell.2018.06.045.

Reference Type BACKGROUND
PMID: 30142345 (View on PubMed)

Forsgren M, Isolauri E, Salminen S, Rautava S. Late preterm birth has direct and indirect effects on infant gut microbiota development during the first six months of life. Acta Paediatr. 2017 Jul;106(7):1103-1109. doi: 10.1111/apa.13837. Epub 2017 Apr 24.

Reference Type BACKGROUND
PMID: 28316118 (View on PubMed)

Korpela K, Helve O, Kolho KL, Saisto T, Skogberg K, Dikareva E, Stefanovic V, Salonen A, Andersson S, de Vos WM. Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study. Cell. 2020 Oct 15;183(2):324-334.e5. doi: 10.1016/j.cell.2020.08.047. Epub 2020 Oct 1.

Reference Type RESULT
PMID: 33007265 (View on PubMed)

Other Identifiers

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HUS/1978/2023

Identifier Type: -

Identifier Source: org_study_id

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