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Not yet recruitingNCT05817448Updated May 24, 2023

Hypoxia-induced Autophagy in the Pathogenesis of MAP

An observational study in Hypoxia, Autophagy and Placenta, sponsored by Assiut University. Not yet recruiting. Open to female participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2023-05-24.

Sponsored by Assiut University · Observational

From the registry’s dates

  • Primary completion was expected by Sep 2024, 2 years 2 months ago, but the record still lists the study as not yet recruiting.
Study type
Observational
Model
Case-control
Time perspective
Cross-sectional
Enrollment
80
Ages
18 Years to 45 Years
Sex
Female
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Study summary

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.

Read the 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.

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Conditions studied

  • Hypoxia
  • Autophagy
  • Placenta
  • Morbidly Adherent Placenta

Keywords

  • HIF1α
  • hypoxia-induced autophagy
  • LC3B
  • invasion-related markers
  • MMP-9
  • Morbidly Adherent Placenta
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In context

Hypoxia

1,076 studies on the registry are indexed under Hypoxia; 213 are open to participants now.

This study's planned enrollment of 80 is close to the median of 79 across 277 observational studies indexed under Hypoxia.

Browse Hypoxia studies →

Lead sponsor

Assiut University is the lead sponsor of 5,078 studies on the registry; 2,178 are open to participants now.

Of its 14 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Female
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,

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
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Study design

Observational model
Case-control
Time perspective
Cross-sectional
Enrollment
80 participants (estimated)
Patient registry
No

Groups and cohorts

  • 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

  • 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

Interventions

  • Diagnostic testHIF 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

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What researchers measure

Primary outcomes

  1. Compare the expression of HIF 1α and LC3B by immunohistochemistry and the level of MMP-9

    To explore the mechanism of abnormal trophoblasts invasion in MAP.

    Time frame: 28-40 weeks of gestation.

Secondary outcomes

  1. Measure MMP-9 concentration in the maternal plasma

    To verify its usefulness as an antenatal predictor of MAP

    Time frame: 28-40 weeks of gestation.

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Study locations

No study locations are listed for this record.

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References and documents

Publications

  • Morfaw F, Fundoh M, Bartoszko J, Mbuagbaw L, Thabane L. Using tocolysis in pregnant women with symptomatic placenta praevia does not significantly improve prenatal, perinatal, neonatal and maternal outcomes: a systematic review and meta-analysis. Syst Rev. 2018 Dec 27;7(1):249. doi: 10.1186/s13643-018-0923-2. PubMed 30591076 ↗
  • Shainker SA, Silver RM, Modest AM, Hacker MR, Hecht JL, Salahuddin S, Dillon ST, Ciampa EJ, D'Alton ME, Otu HH, Abuhamad AZ, Einerson BD, Branch DW, Wylie BJ, Libermann TA, Karumanchi SA. Placenta accreta spectrum: biomarker discovery using plasma proteomics. Am J Obstet Gynecol. 2020 Sep;223(3):433.e1-433.e14. doi: 10.1016/j.ajog.2020.03.019. Epub 2020 Mar 19. PubMed 32199927 ↗
  • Morlando M, Collins S. Placenta Accreta Spectrum Disorders: Challenges, Risks, and Management Strategies. Int J Womens Health. 2020 Nov 10;12:1033-1045. doi: 10.2147/IJWH.S224191. eCollection 2020. PubMed 33204176 ↗
  • Faraji A, Akbarzadeh-Jahromi M, Bahrami S, Gharamani S, Raeisi Shahraki H, Kasraeian M, Vafaei H, Zare M, Asadi N. Predictive value of vascular endothelial growth factor and placenta growth factor for placenta accreta spectrum. J Obstet Gynaecol. 2022 Jul;42(5):900-905. doi: 10.1080/01443615.2021.1955337. Epub 2021 Sep 24. PubMed 34558384 ↗
  • Seno K, Tanikawa N, Takahashi H, Ohkuchi A, Suzuki H, Matsubara S, Iwata H, Kuwayama T, Shirasuna K. Oxygen concentration modulates cellular senescence and autophagy in human trophoblast cells. Am J Reprod Immunol. 2018 Jun;79(6):e12826. doi: 10.1111/aji.12826. Epub 2018 Feb 15. PubMed 29446169 ↗
  • Parrish AR. Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target. Prog Mol Biol Transl Sci. 2017;148:31-65. doi: 10.1016/bs.pmbts.2017.03.001. Epub 2017 May 4. PubMed 28662825 ↗
  • Chen Y, Wang L, Bao J, Sha X, Cui L, Huang Q, Gu C, Li X, Liu H. Persistent hypoxia induced autophagy leading to invasiveness of trophoblasts in placenta accreta. J Matern Fetal Neonatal Med. 2021 Apr;34(8):1297-1303. doi: 10.1080/14767058.2019.1635582. Epub 2019 Jul 3. PubMed 31269830 ↗
  • Nakashima A, Tsuda S, Kusabiraki T, Aoki A, Ushijima A, Shima T, Cheng SB, Sharma S, Saito S. Current Understanding of Autophagy in Pregnancy. Int J Mol Sci. 2019 May 11;20(9):2342. doi: 10.3390/ijms20092342. PubMed 31083536 ↗
  • Nakashima A, Aoki A, Kusabiraki T, Cheng SB, Sharma S, Saito S. Autophagy regulation in preeclampsia: Pros and cons. J Reprod Immunol. 2017 Sep;123:17-23. doi: 10.1016/j.jri.2017.08.006. Epub 2017 Aug 26. PubMed 28869810 ↗
  • El-Hussieny M, Mohammed EM, Zenhom NM, Refaie MM, Okasha AM, Tawab MAE. Possible Role of TGF-beta1, MMP-2, E-CAD, beta-Catenin and Antioxidants in Pathogenesis of Placenta Accreta. Fetal Pediatr Pathol. 2021 Jun;40(3):222-232. doi: 10.1080/15513815.2020.1843574. Epub 2020 Nov 11. PubMed 33172328 ↗
  • Gao F, Zhou C, Qiu W, Wu H, Li J, Peng J, Qiu M, Liang C, Gao J, Luo S. Total flavonoids from Semen Cuscutae target MMP9 and promote invasion of EVT cells via Notch/AKT/MAPK signaling pathways. Sci Rep. 2018 Nov 26;8(1):17342. doi: 10.1038/s41598-018-35732-6. PubMed 30478366 ↗
  • Fratelli N, Prefumo F, Maggi C, Cavalli C, Sciarrone A, Garofalo A, Viora E, Vergani P, Ornaghi S, Betti M, Vaglio Tessitore I, Cavaliere AF, Buongiorno S, Vidiri A, Fabbri E, Ferrazzi E, Maggi V, Cetin I, Frusca T, Ghi T, Kaihura C, Di Pasquo E, Stampalija T, Belcaro C, Quadrifoglio M, Veneziano M, Mecacci F, Simeone S, Locatelli A, Consonni S, Chianchiano N, Labate F, Cromi A, Bertucci E, Facchinetti F, Fichera A, Granata D, D'Antonio F, Foti F, Avagliano L, Bulfamante GP, Cali G; ADoPAD (Antenatal Diagnosis of Placental Adhesion Disorders) Working Group. Third-trimester ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from the ADoPAD study. Ultrasound Obstet Gynecol. 2022 Sep;60(3):381-389. doi: 10.1002/uog.24889. PubMed 35247287 ↗
  • world health organisation. Rising rates suggest increasing numbers of medically unnecessary, potentially harmful procedures 2021 [cited 16 june 2021
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 24, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT05817448
Lead sponsor
Assiut University
Responsible party
Nermeen Bahaa El Dien Mohamed Ahmed (Demonstrator at Physiology department, Assiut University) — Principal investigator
First posted
Apr 18, 2023
Start date
Sep 2023 (estimated)
Primary completion
Sep 2024 (estimated)
Completion
Nov 2024 (estimated)
Last update
May 24, 2023

Study contacts

Nermeen Bahaa ElDien Mohamed Ahmed, dr
Contact
nermeenbahaa11@gmail.com
01011126294
Dalia Gamal El-Din Mostafa Morsy, prof dr
Contact
dalia_gamal66@yahoo.com
01111948221

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in May 2023. You cannot join it, but the record below documents what was studied.

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