Serum Soluble Endoglin and Matrix Metalloproteinase 14 With Elisa Method in Early/Late-onset Preeclampsia

• ClinicalTrials.gov Identifier: NCT03932877
• Recruitment Status: Completed
• First Posted: May 1, 2019
• Last Update Posted: May 2, 2019
• Sponsor: Cengiz Gokcek Women's and Children's Hospital
• Information provided by (Responsible Party): Ali Ovayolu, Cengiz Gokcek Women's and Children's Hospital

Study Description

Brief Summary:

Objective: Defective placentation and inadequate trophoblastic invasion have an important place in the aetiology of preeclampsia (PrE). Trophoblasts invade the maternal decidua and remodel spiral arteries with matrix metalloproteinase-14 (MMP-14). To the best of our knowledge, studies of MMP-14 protein levels of PrE patients' sera remain unpublished. This study aims to investigate the value of serum MMP-14 and soluble endoglin (s-ENG) in PrE patients and healthy controls.

Methods: The study was conducted with 30 late-onset preeclampsia patients (L-PrE) as group1 (gestational age≥34 weeks), 33 patients with normal pregnancies as group2 (gestational age≥34 weeks), 31 early-onset preeclampsia patients (E-PrE) as group3 (gestational age<34 weeks), and 31 patients with normal pregnancies as group 4 (gestational age<34 weeks). Serum MMP-14 and s-ENG levels measured by ELISA were compared.

Condition or disease	Intervention/treatment
Preeclampsia	Other: MMP-14 and s-ENG levels

Detailed Description:

The study was conducted at Cengiz Gokcek Women's and Children's Hospital, Gaziantep, Turkey at department of obstetrics and gynecology between date of January 2018 and December 2018. The study protocol was designed according to the Declaration of Helsinki, and the institutional ethical review board of Gaziantep University approved the study (Reference number: 2018/91). One hundred twenty-five women enrolled in the study in four groups. The investigators consecutively recruited 61 pregnancies complicated with preeclampsia, and 64 healthy pregnancies will select for the control group. All participiants gave their oral and written informed consent before their inclusion in the study.

Study Design

• Study Type: Observational
• Actual Enrollment: 125 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: An Analysis Soluble Endoglin and Matrix Metalloproteinase 14 With Elisa Method in the Diagnosis and Severity of Early/Late-onset Preeclampsia
• Actual Study Start Date: January 30, 2018
• Actual Primary Completion Date: November 30, 2018
• Actual Study Completion Date: December 30, 2018

Groups and Cohorts

Group/Cohort	Intervention/treatment
late-onset preeclampsia, group1; 30 late-onset preeclampsia patients as group1 (gestational age≥34 weeks). The diagnosis of preeclampsia, as defined by the Committee on Terminology of the American College of Obstetricians and Gynecologists (ACOG), will establish based on the presence of proteinuria (urinary excretion of 300 mg protein or higher, or at least 1+in dipstick in a 24-h urine specimen) and a blood pressure level of ≥140/90mmHg (two blood pressure measurements 6 h apart) that occurs after 20 weeks of gestation in a previously normotensive woman. Diastolic and/or systolic blood pressure up to 110/160 mm Hg will consider mild, and higher values will consider to being severe.	Other: MMP-14 and s-ENG levels; Venous blood sampled from the antecubital veins for measuring the serum concentration of MMP-14 and s-ENG levels. The serum MMP-14 and s-ENG levels measured using commercially available reagent kits, which is produced to detect human MMP-14 and s-ENG levels (Rel Assay Diagnostics Gaziantep, Turkey). The MMP-14 and s-ENG levels measurements were performed in accordance with the company's protocol.
Control, group 2; 33 patients with normal pregnancies as group2 (gestational age≥34 weeks). The control groups' samples obtained during the routine obstetrical care examination in the third trimester of pregnancy. Then these pregnant women followed-up until the delivery.	Other: MMP-14 and s-ENG levels; Venous blood sampled from the antecubital veins for measuring the serum concentration of MMP-14 and s-ENG levels. The serum MMP-14 and s-ENG levels measured using commercially available reagent kits, which is produced to detect human MMP-14 and s-ENG levels (Rel Assay Diagnostics Gaziantep, Turkey). The MMP-14 and s-ENG levels measurements were performed in accordance with the company's protocol.
early-onset preeclampsia, group 3; 31 early-onset preeclampsia patients as group3 (gestational age<34 weeks). The diagnosis of preeclampsia, as defined by the Committee on Terminology of the American College of Obstetricians and Gynecologists (ACOG), will establish based on the presence of proteinuria (urinary excretion of 300 mg protein or higher, or at least 1+in dipstick in a 24-h urine specimen) and a blood pressure level of ≥140/90mmHg (two blood pressure measurements 6 h apart) that occurs after 20 weeks of gestation in a previously normotensive woman. Diastolic and/or systolic blood pressure up to 110/160 mm Hg considered mild, and higher values considered to being severe.	Other: MMP-14 and s-ENG levels; Venous blood sampled from the antecubital veins for measuring the serum concentration of MMP-14 and s-ENG levels. The serum MMP-14 and s-ENG levels measured using commercially available reagent kits, which is produced to detect human MMP-14 and s-ENG levels (Rel Assay Diagnostics Gaziantep, Turkey). The MMP-14 and s-ENG levels measurements were performed in accordance with the company's protocol.
Control, group 4; 31 patients with normal pregnancies as group 4 (gestational age<34 weeks). The control groups' samples obtained during the routine obstetrical care examination in the third trimester of pregnancy. Then these pregnant women followed-up until the delivery.	Other: MMP-14 and s-ENG levels; Venous blood sampled from the antecubital veins for measuring the serum concentration of MMP-14 and s-ENG levels. The serum MMP-14 and s-ENG levels measured using commercially available reagent kits, which is produced to detect human MMP-14 and s-ENG levels (Rel Assay Diagnostics Gaziantep, Turkey). The MMP-14 and s-ENG levels measurements were performed in accordance with the company's protocol.

Outcome Measures

Primary Outcome Measures :

1. Serum matrix metalloproteinase-14 levels in preeclampsia [ Time Frame: 1 day ]
   The primary endpoint in this analysis is to evaluate the value of serum matrix metalloproteinase-14 levels (ng/ml) in preeclampsia patients and also address its relationship with its severity.

Secondary Outcome Measures :

1. Serum soluble endoglin levels in preeclampsia [ Time Frame: 1 day ]
   The secondary endpoint in this analysis is to evaluate the value of serum soluble endoglin levels (ng/ml) in preeclampsia patients and also address its relationship with its severity.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: pregnancy. Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, most often the liver and kidneys. Preeclampsia usually begins after 20 weeks of pregnancy in women whose blood pressure had been normal. Early-onset preeclampsia is usually defined as preeclampsia that develops before 34 weeks of gestation, whereas late-onset preeclampsia develops at or after 34 weeks of gestation.
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

The investigators consecutively will recruite 61 subjects with preeclampsia, and 64 healthy preganancies will selecte for the control group.

Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, most often the liver and kidneys. Preeclampsia usually begins after 20 weeks of pregnancy in women whose blood pressure had been normal. Early-onset preeclampsia is usually defined as preeclampsia that develops before 34 weeks of gestation, whereas late-onset preeclampsia develops at or after 34 weeks of gestation.

Criteria

Inclusion Criteria:

• preeclampsia
• healthy pregnancy

Exclusion Criteria:

• pregnant women with any systemic condition (such as chronic hypertension, diabetes mellitus, thyroid diseases, liver and kidney diseases)
• women with a history of drug use throughout pregnancy
• history of medication for PE treatment at the time of first admission
• patients who had fetal congenital abnormalities or genetic syndromes
• multiple gestations
• active labour

Contacts and Locations

Locations

Turkey

Cengiz Gokcek Women's and Child's hospital

Gaziantep, Turkey

Sponsors and Collaborators

Cengiz Gokcek Women's and Children's Hospital

Investigators

• Principal Investigator: Ali Ovayolu; Cengiz Gokcek WCH

  Study Documents (Full-Text)

Documents provided by Ali Ovayolu, Cengiz Gokcek Women's and Children's Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] June 6, 2018

More Information

Publications of Results:

Zhang XH, Zhang HY, Lu S, Jiang LL, Wu J, Yang YL, Zhang SA. MMP-14 aggravates onset of severe preeclampsia by mediating soluble endoglin release. Eur Rev Med Pharmacol Sci. 2018 Mar;22(5):1209-1215. doi: 10.26355/eurrev_201803_14460.

Espino Y Sosa S, Flores-Pliego A, Espejel-Nuñez A, Medina-Bastidas D, Vadillo-Ortega F, Zaga-Clavellina V, Estrada-Gutierrez G. New Insights into the Role of Matrix Metalloproteinases in Preeclampsia. Int J Mol Sci. 2017 Jul 20;18(7). pii: E1448. doi: 10.3390/ijms18071448. Review.

Kaitu'u-Lino TJ, Palmer KR, Whitehead CL, Williams E, Lappas M, Tong S. MMP-14 is expressed in preeclamptic placentas and mediates release of soluble endoglin. Am J Pathol. 2012 Mar;180(3):888-894. doi: 10.1016/j.ajpath.2011.11.014. Epub 2012 Jan 31.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ovayolu A, Karaman E, Turgut A, Cekici Y, Ortabag T, Chiara Rapisarda AM, Noventa M, Cianci A. Endothelial cell-specific-molecule-1 (endocan) levels in women with premature ovarian insufficiency: a prospective comparative study. J Obstet Gynaecol. 2021 May;41(4):637-641. doi: 10.1080/01443615.2020.1789952. Epub 2020 Aug 18.

• Responsible Party: Ali Ovayolu, Principal Investigator, Cengiz Gokcek Women's and Children's Hospital
• ClinicalTrials.gov Identifier: NCT03932877
• Other Study ID Numbers: CengizGWCH3
• First Posted: May 1, 2019
• Last Update Posted: May 2, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pre-Eclampsia; Hypertension, Pregnancy-Induced; Pregnancy Complications