PreeclampsiaMATERNCT06421493
Role of the Maternal Microbiota on the Immune Response and Metabolism During Hypertensive Disorders
An observational study of Preeclampsia, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
Preeclampsia (PE) is a significant cause of maternal and fetal morbidity and mortality, characterized by high blood pressure and proteinuria during pregnancy. It has two main phenotypes: one linked to placental damage and the other to metabolic factors like obesity. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Preeclampsia
- How many people
- 300 participants
- Where
- 1 siteItaly
- Study dates
- 6 Jun 2020to 6 Jun 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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
- Adult, Older adult
Study population: Women with pregnancies complicated by hypertensive disorders associated with or without fetal growth restriction in the second and third trimesters, and women identified as high-risk for the development of preeclampsia from the first trimester of pregnancy, will be offered the opportunity to participate in the study. To obtain a control sample, equal participation (1:1 ratio) of pregnant women identified as low-risk in first-trimester screening for preeclampsia and fetal growth restriction, who will undergo physiological follow-up visits until delivery, will also be requested. Recruitment of controls will follow an alternating principle: high risk-low risk-high risk-low risk. Patients will be followed up at defined intervals, varying depending on the underlying condition. High-risk patients and controls will be seen once per trimester if the pregnancy remains uncomplicated.
Who may be able to join
- Age > 18 years
- Singleton pregnancy
- Live fetus at 11-13 weeks of gestation
- Pregnancies complicated by hypertensive disorders (HDP) and fetal growth restriction (FGR) Women with pregnancies complicated by HDP and a fetus with appropriate weight for gestational age (AGAf)
- Women with pregnancies complicated solely by early fetal growth restriction (before 34 weeks)
- Women with pregnancies complicated solely by late fetal growth restriction (after 34 weeks)
- Women identified as high-risk in first-trimester screening for preeclampsia Women identified as high-risk in first-trimester screening for fetal growth restriction
- Low-risk pregnancies in first-trimester screening for preeclampsia and fetal growth restriction, with physiological follow-up visits until delivery (homogeneous control sample)
Who cannot join
- Multiple pregnancies
- Pregnancies complicated by major fetal abnormalities identified during the 11-13 week gestational assessment
- Women who are unconscious or severely ill, women with learning difficulties, and those with severe psychiatric disorders
- Age <18 years
- Women who have not provided informed consent for the study
- Women with HIV, HBV, HCV infection
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- Women with a history of leukemia and lymphoma
- Women with immunodeficiency
- Women who have used corticosteroids or other immunosuppressants in the last 3 months
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Humanitas University
Pieve Emanuele, Milan, 20072
Silvia Giugliano, PhD, +390282243190, silvia.giugliano@hunimed.eu
Silvia Giugliano, PhD
About this study
Preeclampsia (PE) is a significant cause of maternal and fetal morbidity and mortality, characterized by high blood pressure and proteinuria during pregnancy. It has two main phenotypes: one linked to placental damage and the other to metabolic factors like obesity. Early identification of high-risk groups is crucial, though there's ongoing disagreement over its classification. Research suggests a potential connection between maternal gut bacteria and PE, offering avenues for improved prevention strategies. This study aims to investigate the differences in maternal gut microbiota between these two PE phenotypes.
Read the detailed description
Preeclampsia (PE) is one of the leading causes of maternal and fetal morbidity and mortality. It is defined as the presence of systolic blood pressure (SBP) ≥ 140 and diastolic blood pressure (DBP) ≥ 90 on two consecutive measurements six hours apart, associated with proteinuria >300 mg/24 h or 2++ detected by urine dipstick or the presence of organ damage or intrauterine growth restriction. Preeclampsia complicates 3-8% of pregnancies and is responsible for more than 76,000 maternal deaths annually.
Scientific evidence suggests the existence of two distinct phenotypes of the disease: preeclampsia due to placental damage and preeclampsia on a metabolic basis. The former phenotype recognizes altered invasion of the maternal endometrium by the trophoblast as its pathogenesis, where defective trophoblast invasion leads to the development of preeclampsia often associated with early presentation in pregnancy, intrauterine growth restriction (IUGR), and the need for delivery at low gestational ages. The latter phenotype recognizes a metabolic basis, which represents about 4% of hypertensive disorders of pregnancy (HDP), and is dependent on maternal predisposition in patients with visceral obesity and metabolic syndrome.
Evidence suggests that maternal risk factors for metabolic dysfunction may lead to late placental dysfunction in pregnancy. Metabolic-based preeclampsia manifests in patients with pre-existing low-grade inflammation related to truncal obesity and metabolic syndrome, compounded by pregnancy-related inflammation and insulin resistance.
Today, starting as early as the first trimester of pregnancy, maternal cardiovascular and hemodynamic function can be assessed using a non-invasive and safe method for both the mother and fetus through the USCOM (Ultra Sonic Cardiac Output Monitor) system. This system provides real-time data on numerous central and peripheral hemodynamic parameters.
There is still disagreement among scientific societies regarding the classification of preeclampsia and its possible different clinical phenotypes, making personalized clinical approaches to this condition challenging. However, early identification of high-risk groups is becoming increasingly important for diagnostic follow-up and therapeutic strategies based on pathogenesis.
Recently, a screening method at 11-13 weeks of gestation has been developed to predict 75% of pregnancies that will develop preterm preeclampsia (<37 weeks of gestation) based on a risk calculation algorithm combining weight and height measurements, mean arterial pressure measured with automated devices, blood sampling for PLGF measurement, and Doppler ultrasound measurement of the mean pulsatility index (PI) of the uterine arteries.
However, this screening method can only predict a portion of patients who will develop preeclampsia before 37 weeks and who may benefit from aspirin intake if administered at doses >100mg and before 16 weeks. Predicting and effectively preventing preeclampsia that occurs after 37 weeks remains the subject of debate and scientific research.
Among emerging etiopathogenetic hypotheses, numerous scientific publications suggest that alterations in maternal immunity and immune tolerance are the basis of hypertensive disorders in pregnancy. Recent discoveries suggest that changes in maternal intestinal microbiota may underlie these immune alterations. Alterations in gut microbiota diversity and composition, known as "dysbiosis," can influence systemic immune responses and metabolic disturbances such as gestational diabetes and preeclampsia, posing risks of metabolic alterations in the neonate.
Based on these premises, this study aims to define the characteristics of maternal intestinal microbiota in the two different clinical phenotypes of preeclampsia: placental preeclampsia associated with growth restriction and metabolic-based preeclampsia associated with a fetus of appropriate weight for gestational age.
- Conditions
- Preeclampsia
- Keywords
- microbiome, immune system, metabolome
- Medical subject headings
- Pre-Eclampsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Case group | Age > 18 years Singleton pregnancy Live fetus at 11-13 weeks of gestation Pregnancies complicated by hypertensive disorders (HDP) and fetal growth restriction (FGR) Women with pregnancies complicated by HDP and a fetus with appropriate weight for gestational age (AGAf) Women with pregnancies complicated solely by early fetal growth restriction (before 34 weeks) Women with pregnancies complicated solely by late fetal growth restriction (after 34 weeks) Women identified as high-risk in first-trimester screening for preeclampsia Women identified as high-risk in first-trimester screening for fetal growth restriction | |
| Controls | Age > 18 years Singleton pregnancy Feto vivo a 11-13 settimane di gravidanza Low-risk pregnancies in first-trimester screening for preeclampsia and fetal growth restriction, with physiological follow-up visits until delivery (homogeneous control sample) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study of the Characteristics of Maternal Gut Microbiota in Women with Pregnancies Complicated by Hypertensive Disorders, with or without Fetal Growth Restriction.
Study of the characteristics of the microbiota in fecal samples from women with pregnancies complicated by hypertensive disorders, with or without fetal growth restriction.
Measured: through study completion, an average of 1 year
Study of the Characteristics of Metabolome, in Women with Pregnancies Complicated by Hypertensive Disorders, with or without Fetal Growth Restriction.
Study of the characteristics of the metabolites in fecal and blood samples from women with pregnancies complicated by hypertensive disorders, with or without fetal growth restriction.
Measured: through study completion, an average of 1 year
Study of the Characteristics of NK and B Cells in Women with Pregnancies Complicated by Hypertensive Disorders, with or without Fetal Growth Restriction.
Study of the characteristics of NK and B cells in blood samples from women with pregnancies complicated by hypertensive disorders, with or without fetal growth restriction.
Measured: through study completion, an average of 1 year
Secondary outcomes (4)
Study of the Characteristics of Microbiota in Women with Pregnancies
Assessment of Changes in Maternal Microbiota, in High-Risk Patients in the First Trimester for Preeclampsia or Fetal Growth Restriction
Measured: through study completion, an average of 1 year
Study of the Evolution of Metabolome in Women with Pregnancies
Assessment of Changes in Maternal Metabolites in High-Risk Patients in the First Trimester for Preeclampsia or Fetal Growth Restriction
Measured: through study completion, an average of 1 year
Study of the Evolution of NK and B Cells in Women with Pregnancies
Assessment of Changes in B and NK Cells in High-Risk Patients in the First Trimester for Preeclampsia or Fetal Growth Restriction
Measured: through study completion, an average of 1 year
Evaluation of a Possible Correlation Between Dietary Habits and Maternal Gut Microbiota
The diet record will be obtained through a validated questionnaire on dietary habits and lifestyle. Spearman correlation of α-diversity microbiota measures and dietary intake will be performed.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2024
- Study start6 Jun 2020
- Primary completion6 Jun 2025 (estimated)
- Study completion6 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PreeclampsiaStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06421493
- Sponsor's protocol ID
- 0004622
- Acronym
- MATER
- Status last verified
- May 2024
- First submitted
- 7 May 2024
- Last updated
- 20 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of the Maternal Microbiota on the Immune Response and Metabolism During Hypertensive Disorders
- ClinicalTrials.gov ID
- NCT06421493
- Acronym / sponsor ID
- MATER / 0004622
- Conditions
- Preeclampsia
- Keywords
- microbiome, immune system, metabolome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Collaborators
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Study start
- 6 Jun 2020 (actual)
- Primary completion
- 6 Jun 2025 (estimated)
- Study completion
- 6 Jun 2025 (estimated)
- First posted
- 20 May 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.
Preeclampsia (PE) is a significant cause of maternal and fetal morbidity and mortality, characterized by high blood pressure and proteinuria during pregnancy. It has two main phenotypes: one linked to placental damage and the other to metabolic factors like obesity. Early identification of high-risk groups is crucial, though there's ongoing disagreement over its classification. Research suggests a potential connection between maternal gut bacteria and PE, offering avenues for improved prevention strategies. This study aims to investigate the differences in maternal gut microbiota between these two PE phenotypes.
Detailed description
Preeclampsia (PE) is one of the leading causes of maternal and fetal morbidity and mortality. It is defined as the presence of systolic blood pressure (SBP) ≥ 140 and diastolic blood pressure (DBP) ≥ 90 on two consecutive measurements six hours apart, associated with proteinuria >300 mg/24 h or 2++ detected by urine dipstick or the presence of organ damage or intrauterine growth restriction. Preeclampsia complicates 3-8% of pregnancies and is responsible for more than 76,000 maternal deaths annually.
Scientific evidence suggests the existence of two distinct phenotypes of the disease: preeclampsia due to placental damage and preeclampsia on a metabolic basis. The former phenotype recognizes altered invasion of the maternal endometrium by the trophoblast as its pathogenesis, where defective trophoblast invasion leads to the development of preeclampsia often associated with early presentation in pregnancy, intrauterine growth restriction (IUGR), and the need for delivery at low gestational ages. The latter phenotype recognizes a metabolic basis, which represents about 4% of hypertensive disorders of pregnancy (HDP), and is dependent on maternal predisposition in patients with visceral obesity and metabolic syndrome.
Evidence suggests that maternal risk factors for metabolic dysfunction may lead to late placental dysfunction in pregnancy. Metabolic-based preeclampsia manifests in patients with pre-existing low-grade inflammation related to truncal obesity and metabolic syndrome, compounded by pregnancy-related inflammation and insulin resistance.
Today, starting as early as the first trimester of pregnancy, maternal cardiovascular and hemodynamic function can be assessed using a non-invasive and safe method for both the mother and fetus through the USCOM (Ultra Sonic Cardiac Output Monitor) system. This system provides real-time data on numerous central and peripheral hemodynamic parameters.
There is still disagreement among scientific societies regarding the classification of preeclampsia and its possible different clinical phenotypes, making personalized clinical approaches to this condition challenging. However, early identification of high-risk groups is becoming increasingly important for diagnostic follow-up and therapeutic strategies based on pathogenesis.
Recently, a screening method at 11-13 weeks of gestation has been developed to predict 75% of pregnancies that will develop preterm preeclampsia (<37 weeks of gestation) based on a risk calculation algorithm combining weight and height measurements, mean arterial pressure measured with automated devices, blood sampling for PLGF measurement, and Doppler ultrasound measurement of the mean pulsatility index (PI) of the uterine arteries.
However, this screening method can only predict a portion of patients who will develop preeclampsia before 37 weeks and who may benefit from aspirin intake if administered at doses >100mg and before 16 weeks. Predicting and effectively preventing preeclampsia that occurs after 37 weeks remains the subject of debate and scientific research.
Among emerging etiopathogenetic hypotheses, numerous scientific publications suggest that alterations in maternal immunity and immune tolerance are the basis of hypertensive disorders in pregnancy. Recent discoveries suggest that changes in maternal intestinal microbiota may underlie these immune alterations. Alterations in gut microbiota diversity and composition, known as "dysbiosis," can influence systemic immune responses and metabolic disturbances such as gestational diabetes and preeclampsia, posing risks of metabolic alterations in the neonate.
Based on these premises, this study aims to define the characteristics of maternal intestinal microbiota in the two different clinical phenotypes of preeclampsia: placental preeclampsia associated with growth restriction and metabolic-based preeclampsia associated with a fetus of appropriate weight for gestational age.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case group | – | –Age > 18 years Singleton pregnancy Live fetus at 11-13 weeks of gestation Pregnancies complicated by hypertensive disorders (HDP) and fetal growth restriction (FGR) Women with pregnancies complicated by HDP and a fetus with appropriate weight for gestational age (AGAf) Women with pregnancies complicated solely by early fetal growth restriction (before 34 weeks) Women with pregnancies complicated solely by late fetal growth restriction (after 34 weeks) Women identified as high-risk in first-trimester screening for preeclampsia Women identified as high-risk in first-trimester screening for fetal growth restriction |
| Controls | – | –Age > 18 years Singleton pregnancy Feto vivo a 11-13 settimane di gravidanza Low-risk pregnancies in first-trimester screening for preeclampsia and fetal growth restriction, with physiological follow-up visits until delivery (homogeneous control sample) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Age groups
- Adult, Older adult
- Study population
- Women with pregnancies complicated by hypertensive disorders associated with or without fetal growth restriction in the second and third trimesters, and women identified as high-risk for the development of preeclampsia from the first trimester of pregnancy, will be offered the opportunity to participate in the study. To obtain a control sample, equal participation (1:1 ratio) of pregnant women identified as low-risk in first-trimester screening for preeclampsia and fetal growth restriction, who will undergo physiological follow-up visits until delivery, will also be requested. Recruitment of controls will follow an alternating principle: high risk-low risk-high risk-low risk. Patients will be followed up at defined intervals, varying depending on the underlying condition. High-risk patients and controls will be seen once per trimester if the pregnancy remains uncomplicated.
Key inclusion criteria (8 listed)
- Age > 18 years
- Singleton pregnancy
- Live fetus at 11-13 weeks of gestation
- Pregnancies complicated by hypertensive disorders (HDP) and fetal growth restriction (FGR) Women with pregnancies complicated by HDP and a fetus with appropriate weight for gestational age (AGAf)
- Women with pregnancies complicated solely by early fetal growth restriction (before 34 weeks)
Key exclusion criteria (9 listed)
- Multiple pregnancies
- Pregnancies complicated by major fetal abnormalities identified during the 11-13 week gestational assessment
- Women who are unconscious or severely ill, women with learning difficulties, and those with severe psychiatric disorders
- Age <18 years
- Women who have not provided informed consent for the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Study of the Characteristics of Maternal Gut Microbiota in Women with Pregnancies Complicated by Hypertensive Disorders, with or without Fetal Growth Restriction.
Time frame: through study completion, an average of 1 year
Study of the characteristics of the microbiota in fecal samples from women with pregnancies complicated by hypertensive disorders, with or without fetal growth restriction.
Study of the Characteristics of Metabolome, in Women with Pregnancies Complicated by Hypertensive Disorders, with or without Fetal Growth Restriction.
Time frame: through study completion, an average of 1 year
Study of the characteristics of the metabolites in fecal and blood samples from women with pregnancies complicated by hypertensive disorders, with or without fetal growth restriction.
Study of the Characteristics of NK and B Cells in Women with Pregnancies Complicated by Hypertensive Disorders, with or without Fetal Growth Restriction.
Time frame: through study completion, an average of 1 year
Study of the characteristics of NK and B cells in blood samples from women with pregnancies complicated by hypertensive disorders, with or without fetal growth restriction.
4 secondary outcomes
Study of the Characteristics of Microbiota in Women with Pregnancies
Time frame: through study completion, an average of 1 year
Study of the Evolution of Metabolome in Women with Pregnancies
Time frame: through study completion, an average of 1 year
Study of the Evolution of NK and B Cells in Women with Pregnancies
Time frame: through study completion, an average of 1 year
Evaluation of a Possible Correlation Between Dietary Habits and Maternal Gut Microbiota
Time frame: through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2024.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Preeclampsia, run by Istituto Clinico Humanitas at 1 site in Italy.
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 8 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 20 May 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Study of the Characteristics of Maternal Gut Microbiota in Women with Pregnancies Complicated by Hypertensive Disorders, with or without Fetal Growth Restriction. (time frame: through study completion, an average of 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 May 2024.