Pre-EclampsiaNCT04287998
Role and Expression of MXRA5 in Placental Connective Tissue Remodelling in Preeclampsia
An observational study of Pre-Eclampsia, run by Assiut University.
Trial summary
1. To measure the level of expression of MXRA5 and ANXA4 genes in preeclampsia (PE). 2. To detect the effect of heavy metals (lead (Pb) and arsenic (AR)) on these two genes in the pathology of PE. 3. Read more about this study
- Who is it for?
- Ages 20 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pre-Eclampsia
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2020to 1 May 2021
- 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 20 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: • Placental tissue samples (surgically obtained during the caesarean section from 50 pregnant women) will be selected: * 25 PE patients undergoing caesarean section following diagnosis by blood pressure measurement and urine analysis. * 25 controls undergoing caesarean section. * Placental samples are 4x6 cm in dimension. Blood samples: Six milliliters of maternal blood was collected in plastic tubes. Urinary samples.
Who may be able to join
- Gestational age is >28 weeks.
- Clinically diagnosed PE with blood pressure (≥140/90 mmHg) and proteinuria (≥300mg/dl).
- Healthy pregnant women (age matched control group).
Who cannot join
- Gestational diabetes.
- Pregestational hypertension (essential hypertension) or proteinuria.
- Systemic illness.
- Vaginal infection.
- Major known fetal or chromosomal anomalies.
- Multiple gestations.
Show all 14Show fewer
- Intrauterine infections.
- Preterm premature rupture of membranes.
- Sepsis.
- Fever.
- Colitis ulcerosa.
- Crohn's disease.
- Chronic renal disease.
- Rheumatic disease.
Trial locations and contacts
No sites are listed yet.
Mona A El Baz, Professor contact
About this study
Official title: Role and Expression of Matrix-remodelling Associated 5 Protein (MXRA5) in Connective Tissue Remodelling of Placenta in Preeclampsia
- To measure the level of expression of MXRA5 and ANXA4 genes in preeclampsia (PE).
- To detect the effect of heavy metals (lead (Pb) and arsenic (AR)) on these two genes in the pathology of PE.
- To explore the association of the previous two genes with the heavy metals in link with Phosphoinositide 3-kinases/Protein Kinase B (PI3K/AKT) pathway.
- To detect Syndecan-1 by immunohistochemical antibodies.
- To define the role of extracellular matrix remodelling in PE.
Read the detailed description
- Preeclampsia (PE) is a diverse multisystem syndrome defined as a new onset of hypertension along with evidence of significant multiorgan dysfunction in previously normotensive women 20 weeks of gestation (1)
- The incidence of PE is around 2 - 8 % of pregnancies and it causes about 50,000 deaths worldwide every year (2).
- In Egypt, it complicates 6% - 8% of pregnancies (3).
- Placentation processes include trophoblastic invasion, vascularization of trophoblast to establish and maintain feto-placental vasculature, and subsequent maternal vascular remodeling (4). Extravillous trophoblastic (EVT) cells are crucial for this process (5). If the function of extravillous trophoblast cells is deficient, it can result in PE (6).
- PI3K/AKT pathway plays important roles in placental development and fetal growth (7). PI3K/AKT signaling pathway is important for cell proliferation, migration, invasion and glycolysis/gluconeogenesis (8). AKT can further activate different downstream factors, which plays a predominant role in angiogenesis, vascular permeability and migration (9).
- Matrix metalloproteinase (MMPs) are essential proteases for trophoblast invasion and migration as they promote degrading of the extracellular matrix improving the the cell invasion, while the tissue inhibitors of matrix metalloproteinases (TIMPs) are normal tissue proteins that inhibit the action of MMPs (10).
- Annexin A4 (ANXA4) has been shown to participate in regulation of cellular growth, invasion, and apoptosis. ANXA4 has role in many forms of cancer (11). It was found that ANXA4 expression was downregulated in PE placentas compared with the normal placentas. However, the exact role of ANXA4 in the invasion and survival of trophoblast cells remains less understood.
- ANXA4 binds to the plasma membrane in a Ca2+- dependent manner and regulates its downstream signaling transduction, including phosphoinositide-3-kinase PI3K/AKT signalling (12).
- Matrix-remodelling associated 5 (MXRA5) is a member of the MXRA protein family, participating in cell adhesion and extracellular matrix remodelling (13). This protein is expressed in primates but not in rat or mouse. The function of this protein remains elusive. It resembles the vascular endothelial growth factor (VEGF) receptor and has anti-inflammatory and anti-fibrotic properties (14). Somatic mutations of MXRA5 are found in non-small cell lung cancer and in colorectal cancer (15).
- The expression of MXRA5 was shown to be downregulated in the placentae of PE patients which consequently leads to the inhibition of PI3k/AKT pathway (16).
- As regard that both of ANXA4 and MXRA5 downregulate PI3k/AKT pathway, they are associated to be linked to the pathogenesis of PE.
- Endothelial glycocalyx (EG), the most important protective structure of the endothelium, is an external layer of endothelial cells composed of different proteoglycans (PGs), glycoproteins, glycolipids, and glycosaminoglycans (GAGs). The protective role of EG for endothelium includes for example maintenance of tissue integrity, prevention of leukocytes and platelet adhesion and antithrombotic activity (17). Examples of clinical consequences of EG damage are albuminuria and edema (18).
- Syndecan-1 (SDC-1) is one of the important PGs of EG (19).
- Lead (Pb) is a widespread heavy metal pollutant. Excess Pb in the environment is usually produced via anthropogenic activities, such as mining and untreated sewage irrigation water (20).
- Arsenic (Ar) is a major toxicant in the environment, and a high level of exposure carries an increased risk of cancers and many disorders (21).
- Both of lead and arsenic have been proven to inhibit the PI3K/AKT pathway (22), (23). In this study, lead (Pb) and arsenic (Ar) will be linked to PE through inhibition of PI3K/AKT pathway.
- Conditions
- Pre-Eclampsia
- Keywords
- MXRA5, ANXA4, Syndecan1, TIMP1, lead, arsenic
- 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 |
|---|---|---|
| 1 | PE group | |
| 2 | Control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gene expression level of MXRA5 gene in PE patients and control group
Measured: 1 year
Secondary outcomes (4)
Gene expression level of ANXA4 in PE patients and control group.
Measured: 1 year
Gene expression level of TIMP1 gene in PE patients and control group.
Measured: 1 year
Protein level measurement of phosphorylated AKT(pAKT) in PE patients and control group.
Measured: 1 year
Measurement of lead and arsenic level in PE patients and control group.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2020
- Study start1 Apr 2020 (estimated)
- Primary completion1 Apr 2021 (estimated)
- Study completion1 May 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pre-EclampsiaStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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
- Cross-sectional
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shimaa Ahmed Abdelrahman, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04287998
- Sponsor's protocol ID
- MXRA5 in preeclampsia
- Status last verified
- Feb 2020
- First submitted
- 22 Feb 2020
- Last updated
- 27 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role and Expression of Matrix-remodelling Associated 5 Protein (MXRA5) in Connective Tissue Remodelling of Placenta in Preeclampsia
- ClinicalTrials.gov ID
- NCT04287998
- Acronym / sponsor ID
- MXRA5 in preeclampsia
- Conditions
- Pre-Eclampsia
- Keywords
- MXRA5, ANXA4, Syndecan1, TIMP1, lead, arsenic
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Apr 2020 (estimated)
- Primary completion
- 1 Apr 2021 (estimated)
- Study completion
- 1 May 2021 (estimated)
- First posted
- 27 Feb 2020 (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.
- To measure the level of expression of MXRA5 and ANXA4 genes in preeclampsia (PE).
- To detect the effect of heavy metals (lead (Pb) and arsenic (AR)) on these two genes in the pathology of PE.
- To explore the association of the previous two genes with the heavy metals in link with Phosphoinositide 3-kinases/Protein Kinase B (PI3K/AKT) pathway.
- To detect Syndecan-1 by immunohistochemical antibodies.
- To define the role of extracellular matrix remodelling in PE.
Detailed description
- Preeclampsia (PE) is a diverse multisystem syndrome defined as a new onset of hypertension along with evidence of significant multiorgan dysfunction in previously normotensive women 20 weeks of gestation (1)
- The incidence of PE is around 2 - 8 % of pregnancies and it causes about 50,000 deaths worldwide every year (2).
- In Egypt, it complicates 6% - 8% of pregnancies (3).
- Placentation processes include trophoblastic invasion, vascularization of trophoblast to establish and maintain feto-placental vasculature, and subsequent maternal vascular remodeling (4). Extravillous trophoblastic (EVT) cells are crucial for this process (5). If the function of extravillous trophoblast cells is deficient, it can result in PE (6).
- PI3K/AKT pathway plays important roles in placental development and fetal growth (7). PI3K/AKT signaling pathway is important for cell proliferation, migration, invasion and glycolysis/gluconeogenesis (8). AKT can further activate different downstream factors, which plays a predominant role in angiogenesis, vascular permeability and migration (9).
- Matrix metalloproteinase (MMPs) are essential proteases for trophoblast invasion and migration as they promote degrading of the extracellular matrix improving the the cell invasion, while the tissue inhibitors of matrix metalloproteinases (TIMPs) are normal tissue proteins that inhibit the action of MMPs (10).
- Annexin A4 (ANXA4) has been shown to participate in regulation of cellular growth, invasion, and apoptosis. ANXA4 has role in many forms of cancer (11). It was found that ANXA4 expression was downregulated in PE placentas compared with the normal placentas. However, the exact role of ANXA4 in the invasion and survival of trophoblast cells remains less understood.
- ANXA4 binds to the plasma membrane in a Ca2+- dependent manner and regulates its downstream signaling transduction, including phosphoinositide-3-kinase PI3K/AKT signalling (12).
- Matrix-remodelling associated 5 (MXRA5) is a member of the MXRA protein family, participating in cell adhesion and extracellular matrix remodelling (13). This protein is expressed in primates but not in rat or mouse. The function of this protein remains elusive. It resembles the vascular endothelial growth factor (VEGF) receptor and has anti-inflammatory and anti-fibrotic properties (14). Somatic mutations of MXRA5 are found in non-small cell lung cancer and in colorectal cancer (15).
- The expression of MXRA5 was shown to be downregulated in the placentae of PE patients which consequently leads to the inhibition of PI3k/AKT pathway (16).
- As regard that both of ANXA4 and MXRA5 downregulate PI3k/AKT pathway, they are associated to be linked to the pathogenesis of PE.
- Endothelial glycocalyx (EG), the most important protective structure of the endothelium, is an external layer of endothelial cells composed of different proteoglycans (PGs), glycoproteins, glycolipids, and glycosaminoglycans (GAGs). The protective role of EG for endothelium includes for example maintenance of tissue integrity, prevention of leukocytes and platelet adhesion and antithrombotic activity (17). Examples of clinical consequences of EG damage are albuminuria and edema (18).
- Syndecan-1 (SDC-1) is one of the important PGs of EG (19).
- Lead (Pb) is a widespread heavy metal pollutant. Excess Pb in the environment is usually produced via anthropogenic activities, such as mining and untreated sewage irrigation water (20).
- Arsenic (Ar) is a major toxicant in the environment, and a high level of exposure carries an increased risk of cancers and many disorders (21).
- Both of lead and arsenic have been proven to inhibit the PI3K/AKT pathway (22), (23). In this study, lead (Pb) and arsenic (Ar) will be linked to PE through inhibition of PI3K/AKT pathway.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –PE group |
| 2 | – | –Control group |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- • Placental tissue samples (surgically obtained during the caesarean section from 50 pregnant women) will be selected: * 25 PE patients undergoing caesarean section following diagnosis by blood pressure measurement and urine analysis. * 25 controls undergoing caesarean section. * Placental samples are 4x6 cm in dimension. Blood samples: Six milliliters of maternal blood was collected in plastic tubes. Urinary samples.
Key inclusion criteria (3 listed)
- Gestational age is >28 weeks.
- Clinically diagnosed PE with blood pressure (≥140/90 mmHg) and proteinuria (≥300mg/dl).
- Healthy pregnant women (age matched control group).
Key exclusion criteria (14 listed)
- Gestational diabetes.
- Pregestational hypertension (essential hypertension) or proteinuria.
- Systemic illness.
- Vaginal infection.
- Major known fetal or chromosomal anomalies.
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
Gene expression level of MXRA5 gene in PE patients and control group
Time frame: 1 year
4 secondary outcomes
Gene expression level of ANXA4 in PE patients and control group.
Time frame: 1 year
Gene expression level of TIMP1 gene in PE patients and control group.
Time frame: 1 year
Protein level measurement of phosphorylated AKT(pAKT) in PE patients and control group.
Time frame: 1 year
Measurement of lead and arsenic level in PE patients and control group.
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2020.
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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.
Mona A El Baz, Professor contact
Questions about this trial
What is this clinical trial studying?
An observational study of Pre-Eclampsia, run by Assiut University.
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 3 inclusion and 14 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 27 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Contact Shimaa A Abd Elrahman, assistant lecturer (01069873568, shimo_ahmed_89@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gene expression level of MXRA5 gene in PE patients and control group (time frame: 1 year). 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 27 Feb 2020.