Microbial ColonizationPREFLORNCT06227845
Preterm Infant Intestinal Microbiota Development and Maternal Fecal Transplant
A study testing Fecal microbiota transplant in people with Microbial Colonization, run by Otto Helve at 1 site in Finland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Microbial Colonization
- What is being tested?
- Fecal microbiota transplant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteFinland
- Study dates
- Feb 2024to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Finland1 site
Helsinki University Hospital
Helsinki, Uusimaa
Noora Carpén, noora.carpen@hus.fi
Samuli Rautava, As. prof, samuli.rautava@hus.fi
About this study
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.
Read the 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.
- Conditions
- Microbial Colonization
- Being tested
- Fecal microbiota transplant
- Keywords
- Premature infant, Fecal microbiota transplant, Cesarean section, Immune system development
- Medical subject headings
- Communicable Diseases, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal microbiota transplantOther
0.1-0.3 ml liquid containing 3.5 mg/ml of maternal fecal content, (0.35mg/kg)
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | 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. Receives: Other: Fecal microbiota transplant |
| Control | No intervention | 12 infants born by CS (8 to screening negative mothers and 4 to screening positive mothers in case of Blastocystis hominis or Dientamoeba fragilis). |
| Comparison | No intervention | Infants born vaginally to mothers with screening negative or mild pathogene findings (Blastocystis hominis or Dientamoeba fragilis) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety; Incidence of Treatment- Adverse Events eg. infections and increased need for respiratory support
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.
Measured: 3 months
Secondary outcomes (1)
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.
The investigators focus on the diversity, richness, taxonomic diversity, and transfer of specific bacteria from the mother to the newborn.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2024
- Study startFeb 2024 (estimated)
- Primary completionJan 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Microbial ColonizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Otto Helve
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska Institutet, University of Helsinki
- Responsible party
- Sponsor-investigator, Otto Helve, Helsinki University Central Hospital
- Investigators
- Otto Helve, Docent, Principal investigator, University of Helsinki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06227845
- Sponsor's protocol ID
- HUS/1978/2023
- Acronym
- PREFLOR
- Status last verified
- Feb 2024
- First submitted
- 18 Jan 2024
- Last updated
- 15 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36175995Korpela 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.
PubMed 30086431Van 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.
PubMed 31576423Olin 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.
PubMed 30142345Forsgren 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.
PubMed 28316118Korpela 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.
PubMed 33007265
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preterm Infant Intestinal Microbiota Development and Maternal Fecal Transplant
- ClinicalTrials.gov ID
- NCT06227845
- Acronym / sponsor ID
- PREFLOR / HUS/1978/2023
- Conditions
- Microbial Colonization
- Keywords
- Premature infant, Fecal microbiota transplant, Cesarean section, Immune system development
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Otto HelveUniversity, hospital or other
- Collaborators
- Karolinska Institutet, University of Helsinki
- Study start
- Feb 2024 (estimated)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 29 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Other: Fecal microbiota transplant10 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. |
| Control | No intervention | –12 infants born by CS (8 to screening negative mothers and 4 to screening positive mothers in case of Blastocystis hominis or Dientamoeba fragilis). |
| Comparison | No intervention | –Infants born vaginally to mothers with screening negative or mild pathogene findings (Blastocystis hominis or Dientamoeba fragilis) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fecal microbiota transplant0.1-0.3 ml liquid containing 3.5 mg/ml of maternal fecal content, (0.35mg/kg) | Other | Intervention |
Primary outcome
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.
1 secondary outcome
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2024.
- Background: PubMed 36175995Carpen 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.
- Background: PubMed 30086431Korpela 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.
- Background: PubMed 31576423Van 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.
- Background: PubMed 30142345Olin 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.
- Background: PubMed 28316118Forsgren 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.
- Results publication: PubMed 33007265Korpela 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Otto Helve, Docent principal investigator
University of Helsinki
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fecal microbiota transplant in people with Microbial Colonization, run by Otto Helve at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Noora K Carpén, MD (+358 9 4711, noora.carpen@hus.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety; Incidence of Treatment- Adverse Events eg. infections and increased need for respiratory support (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06227845, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2024.