Hypoxia-induced Autophagy in the Pathogenesis of MAP

May 23, 2023 updated by: Nermeen Bahaa El Dien Mohamed Ahmed, Assiut University

The Possible Role of Hypoxia-induced Autophagy and Matrix Metalloproteinase-9 in the Pathogenesis of Morbidly Adherent Placenta.

To investigate the role of HIF 1α and LC3B in the pathogenesis of MAP, to evaluate the role of MMP-9 in the antenatal prediction of MAP, and to compare the expression of HIF1α, LC3B, and level MMP-9 between patients of placenta previa with MAP and patients with normal placentation.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Cesarean section (CS) rate has been rising rapidly in the recent years.One of the complications of repeated CS is placenta previa, an implantation of placenta on or near internal os.

Morbidly adherent placenta (MAP), known also as placenta accreta spectrum, has histopathologic and clinical types. The placenta becomes abnormally adherent to the uterine wall, fails to separate leading to massive blood loss and possible hysterectomy. The risk of MAP in patient with placenta previa increases with repeated CS.

Theories for development of MAP include abnormal trophoblastic invasion of myometrium, abnormal decidualization, neovascularization and reduction of apoptosis of trophobalsts.

In early pregnancy: the trophoblasts invade spiral arteries and reduce blood flow to the placenta 00leading to hypoxia. Hypoxia inducible factor 1 alpha (HIF-1α), a protein involved in cellular adaptation to hypoxia, increases throughout pregnancy and contributes in the invasion of trophoblasts. Excessive invasion in MAP might prolong the hypoxia, increasing the expression of HIF1α.

Autophagy is a process for managing and removing the damaged organelles and cellular proteins in hypoxia. It supports the trophoblasts. Hypoxia induced autophagy markers such as LC3B might be enhanced by MAP.

Matrix metalloproteinase-9 (MMP-9) plays an important role in cell invasion and placental implantation. Disturbance of MMP-9 might alter the trophobalsts invasion resulting in MAP .

The investigators hypothesize that hypoxia, autophagy and invasiveness are linked to the pathophysiology of MAP, so we will assess the expression of HIF1α, LC3B to estimate their role beside MMP-9.

Study Type

Observational

Enrollment (Anticipated)

80

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

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

selected from out patient's clinic of the department of Obstetrics and Gynecology at Assiut University Hospital, Assiut, Egypt,

Description

Inclusion Criteria:

  1. Gestational age: more than 28 weeks up to 40 weeks.
  2. Pregnant women with at least one previous CS.
  3. Singleton pregnancy.
  4. Patient known to have placenta previa by 2D ultrasound.
  5. Heamodynamically stable patient.

Exclusion Criteria:

  1. Multiple pregnancy.
  2. Gestational age less than 28 weeks.
  3. Heamodynamically unstable patient.
  4. Hypertensive disorder with pregnancy.
  5. Gestational diabetes.
  6. IUGR.
  7. Patient with bleeding tendency or using anticoagulant.

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
control group
40 pregnant women with normal placentation having no pregnancy related disorders according to the physical examination and laboratory findings.
Diagnostic test: HIF 1α and LC3B expression and MMP-9 level

5ml of venous blood samples will be taken from all participants at 28-40 weeks of gestation for detcetion of MMP-9 level by Enzyme-Linked Immune Sorbent Assay (ELISA) kit.

Placental tissue sample in the maternal surface will be taken during CS in placenta previa group and similar location in maternal surface will be sampled after placental delivery in control group for histopathology and immunohistochemistry for detection of HIF 1α and LC3B expression
placenta previa group

40 pregnant women that will be diagnosed according to the ultrasound diagnostic criteria.

Then according to the histopathological examination, placenta previa group will be subdivided into 2 groups, placenta previa with MAP and placenta previa without MAP
Diagnostic test: HIF 1α and LC3B expression and MMP-9 level

5ml of venous blood samples will be taken from all participants at 28-40 weeks of gestation for detcetion of MMP-9 level by Enzyme-Linked Immune Sorbent Assay (ELISA) kit.

Placental tissue sample in the maternal surface will be taken during CS in placenta previa group and similar location in maternal surface will be sampled after placental delivery in control group for histopathology and immunohistochemistry for detection of HIF 1α and LC3B expression

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare the expression of HIF 1α and LC3B by immunohistochemistry and the level of MMP-9
Time Frame: 28-40 weeks of gestation.
To explore the mechanism of abnormal trophoblasts invasion in MAP.
28-40 weeks of gestation.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure MMP-9 concentration in the maternal plasma
Time Frame: 28-40 weeks of gestation.
To verify its usefulness as an antenatal predictor of MAP
28-40 weeks of gestation.

Collaborators and Investigators

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

Sponsor

Assiut University

Publications and helpful links

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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 (Anticipated)

September 1, 2023

Primary Completion (Anticipated)

September 1, 2024

Study Completion (Anticipated)

November 1, 2024

Study Registration Dates

First Submitted

April 5, 2023

First Submitted That Met QC Criteria

April 5, 2023

First Posted (Actual)

April 18, 2023

Study Record Updates

Last Update Posted (Actual)

May 24, 2023

Last Update Submitted That Met QC Criteria

May 23, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • hypoxia in MAP

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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