Preterm Infant Intestinal Microbiota Development and Maternal Fecal Transplant (PREFLOR)

February 13, 2024 updated by: Otto Helve
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: Fecal microbiota transplant
0.1-0.3 ml liquid containing 3.5 mg/ml of maternal fecal content, (0.35mg/kg)
No Intervention: 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).
No Intervention: Comparison
Infants born vaginally to mothers with screening negative or mild pathogene findings (Blastocystis hominis or Dientamoeba fragilis)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety; Incidence of Treatment- Adverse Events eg. infections and increased need for respiratory support
Time Frame: 3 months
The primary outcome of the study is safety of the transplantation process. The patients are followed with measurements of markers of inflammation (C-reactive protein (CRP) and blood leucocytes) on the day of transplant and three consecutive days. Clinical symptoms of infection are monitored (such as apnea, tachycardia, fever) as well as symptoms of the gastrointestinal tract (vomiting, diarrhea, feeding intolerance). Any suspected adverse events (such as infections, increased need for respiratory support) are recorded.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The secondary outcome is the difference in heterogeneity of the intestinal microbiome between infants receiving transplant and the control subjects at 3 and 6 months of age.
Time Frame: 6 months
The investigators focus on the diversity, richness, taxonomic diversity, and transfer of specific bacteria from the mother to the newborn.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Otto Helve

Collaborators

Karolinska Institutet
University of Helsinki

Investigators

  • Principal Investigator: Otto Helve, Docent, University of Helsinki

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2024

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

January 18, 2024

First Submitted That Met QC Criteria

January 18, 2024

First Posted (Actual)

January 29, 2024

Study Record Updates

Last Update Posted (Estimated)

February 15, 2024

Last Update Submitted That Met QC Criteria

February 13, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUS/1978/2023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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