Selected Immunological Indicators and Microbiota in Patients With Premature Birth and Preeclampsia (PRIME)

February 29, 2024 updated by: Zdenek Lastuvka, General University Hospital, Prague

The Role of Selected Immunological Indicators and Microbiota in Patients Experiencing Premature Birth and Preeclampsia

The goal is to demonstrate the relationship of the circulating pool of T-regulatory lymphocytes in the mother's peripheral blood with populations in the placentas and to compare with controls, what is the difference in the expression of individual regulatory molecules of T-regulatory lymphocytes according to new paradigms. The proportional and functional characteristics of T-regulatory lymphocytes will be correlated with the composition of the intestinal and vaginal microbiota.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES

The primary objective of this project is to determine the differences between the circulating pool of regulatory Treg subpopulation proportions and the placental populations in patients with preterm birth and preeclampsia. Pilot study was conducted for the primary objective. Another objective is to evaluate the effect of microbiota on the regulation of Treg cells, especially in relation to mechanisms of preterm birth and preeclampsia. With growing knowledge of the role of microbiota, it is considered that the maternal microbiota could significantly influence setting of immunoregulatory responses even prenatally. Since Treg play a key role in regulating the immunological balance and are indispensable for induction and maintenance of peripheral tolerance, the investigators hypothesise that abnormalities in function of this population are important factors in increasing the risk of gestational pathologies (preterm birth and preeclampsia). Such dysregulation is most likely accompanied by disruption of the physiological Treg epigenetic profile which is in turn influenced by aberrant microbiota composition. Better understanding of these processes and identification of positively or negatively participating bacterial species could enable more reliable prediction of risk-pregnancy and allow for modulation of microbiota to be applied preventively.

Premature birth is defined as pregnancy termination before the end of the gestational week 37. It plays a role in 10% of all pregnancies including spontaneous or medically induced labours. The efforts to postpone premature labour are continuously developed to minimise the consequences such as low birth weight and other risk events. Preeclampsia is a serious blood pressure condition that develops during pregnancy. People with preeclampsia often have high blood pressure (hypertension) and high levels of protein in their urine (proteinuria). It plays role in 5% of all pregnancies. Preeclampsia typically develops after the 20th week of pregnancy. It can also affect other organs in the body and be dangerous for both the mother and her unborn child. Therefore, a great number of scientific studies are now focused on the early prediction of premature labour and preeclampsia and on finding a specific parameter to estimate female patients at premature labour and preeclampsia risk.

HYPOTHESIS AND AIMS

Hypothesis 1: Disbalance between tolerogenic T cell subsets (Treg, Th2, Th9 and Th22) and proinflammatory subsets (Th1 and Th17) is a sign of premature birth or preeclampsia.

Specific aim 1: Determine the differences between the circulating and the placental T cell subpopulations in patients with preterm birth and preeclampsia. Previously published analyses of Trees and their phenotypic properties give inconclusive or even contradictory results. For this reason, the investigators propose a more in depth approach combining deep immunophenotyping capable of identifying effector T cell, Treg and NK cell subsets and their qualitative phenotype together with assessment of functional capabilities of Tregs.

Hypothesis 2: Certain bacterial species of microbiota can be identified to modulate epigenetic maintenance of Treg phenotype.

Specific aim 2: Determine the influence of microbiota on the Treg regulation. Exposure to microbiota is one of the most important environmental factors introduced in the perinatal period. The capability of certain probiotic bacterial species to promote immunological tolerance, restrain inflammation and unwanted reactivity is being established in the context of intestinal health. Both bacteria and their metabolic products are known to shape the immune system. By influencing the epigenetic programming they modulate phenotype and function of a variety of immune cells including Tregs. The investigators hypothesise that beneficial bacterial species can be identified to promote appropriate epigenetic maintenance of Treg phenotype, function and stability, and thus support Treg tolerogenic role. On the contrary, certain bacterial species will contribute to Treg epigenetic dysregulation and introduce a more pro-inflammatory environment with functionally deficient Treg cells. To test this hypothesis, the investigators will characterise microbial composition of material collected from the mother by oral, rectal and vaginal swabs during pregnancy and at the time of birth.

CHARACTERISATION OF EXPECTED RESULTS

The main outcome of the project will be to improve the understanding of the regulatory processes taking part in the immune balance in preterm birth and preeclampsia. Special attention will be given to the dynamics and functional characteristics of Treg and their subpopulations, considering the role of maternal microbiota. The obtained results will be presented on both national and international congresses and symposia and also published in international impacted journals.

Study Type

Observational

Enrollment (Estimated)

100

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

  • Czechia
      • Prague, Czechia, 128 08
        • Recruiting
        • Department of Gynaecology, Obstetrics and Neonatology of the First Faculty of Medicine of the Charles University and General University Hospital in Prague
        • Contact:
        • Contact:

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

Accepts Healthy Volunteers

N/A

Sampling Method

Probability Sample

Study Population

Pregnant women

Description

Inclusion Criteria:

  • singletone pregnancy
  • gestational age 9+0 - 12+0
  • history of preeclampsia (PE)
  • history of spontaneous preterm birth (PTL = preterm labour)
  • history of pPROM (preterm premature rupture of membranes).

Exclusion Criteria:

  • uterine malformations
  • gestational age out of 9+0 - 12+0
  • age out of 19-40

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Pregnant women
Singletone pregnancy, gestational age 9+0 - 12+0, history of preeclampsia (PE) or spontaneous preterm birth (PTL = preterm labour) or pPROM (preterm premature rupture of membranes).
Diagnostic test: Peripheral blood collection

The phenotypic characteristics of leukocytes will be compared between the groups to identify immunological markers of women at risk of preterm delivery.

Samples from the controls will be taken to define a baseline for the measured leukocyte populations.

Diagnostic test: Swab sample collection
Oral, vaginal and rectal swabs will be collected and stored for analysis of microbiota at the time of inclusion. At birth, oral, vaginal and rectal swabs and part of the placenta (placental tissue) will be collected for further analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in selected T cell subpopulations in the first trimester associated with subsequent spontaneous preterm birth
Time Frame: 3 years
The phenotypic characteristics of leukocytes will be compared between the two groups of pregnant women to identify immunological markers of preterm delivery. Peripheral blood from age-matched healthy nonpregnant women (N=20) will also be collected to define a baseline for the measured leukocyte populations. Furthermore, the composition of placenta infiltrating lymphocytes will be compared between groups and following delivery.
3 years
Changes in selected T cell subpopulations in the first trimester associated with subsequent pre-eclampsia
Time Frame: 3 years
The phenotypic characteristics of leukocytes will be compared between the two groups of pregnant women to identify immunological markers of pre-eclampsia. Peripheral blood from age-matched healthy nonpregnant women (N=20) will also be collected to define a baseline for the measured leukocyte populations. Furthermore, the composition of placenta infiltrating lymphocytes will be compared between groups and following delivery.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association of maternal microbiota and maternal T regulatory cell populations.
Time Frame: 3 years
At birth, oral, vaginal and rectal swabs and part of the placenta (placental tissue) will be collected for analysis. Microbial composition of the swabs will be analysed using 16S rRNA sequencing analysis of microbiota and put in context with the T-cell regulatory population of the patient.
3 years

Collaborators and Investigators

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

Sponsor

General University Hospital, Prague

Collaborators

Charles University, Czech Republic
Institute of Hematology and Blood Transfusion, Czech Republic

Investigators

  • Principal Investigator: Zdeněk Laštůvka, MD, PhD, General University Hospital in Prague

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 (Actual)

June 30, 2023

Primary Completion (Estimated)

March 30, 2025

Study Completion (Estimated)

March 30, 2025

Study Registration Dates

First Submitted

February 20, 2024

First Submitted That Met QC Criteria

February 20, 2024

First Posted (Actual)

February 28, 2024

Study Record Updates

Last Update Posted (Estimated)

March 1, 2024

Last Update Submitted That Met QC Criteria

February 29, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIP-23-L-04-223

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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