Clinical trial NCT06779916: Autophagy/Apoptosis Balance in Placental Vascular Pathologies
Official title: Study of the Autophagy/Apoptosis Balance in Placental Vascular Pathologies
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Pregnancy Complications
Pre-Eclampsia
Growth Retardation, Intrauterine
Keywords: trophoblasts
autophagy
apoptosis
placenta
pregnancy
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2025-01-17
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: An initial analysis of the data will make it possible to describe the population.

Quantitative variables will be expressed as mean and standard deviation, or median and quartiles. Qualitative variables will be expressed in headcount and percentage.

Brief summary: Pregnancy increases the risk of thrombosis. Placenta-mediated diseases are a risk factor for cardiovascular pathologies and can lead to maternal-fetal morbidity and mortality. It is essential to understand the cellular and molecular mechanisms of dysfunctions at the vascular-placental interface so that systemic vascular risk can be characterized and, ultimately, screened for, on the basis of new markers (targeted preventive management).

Deregulated autophagy could be the starting point for cell death by apoptosis or necrosis leading to complications.

The pathophysiological mechanisms involved in trophoblast apoptosis are incompletely described. This project follows on from the GrossAuTop-1 study, which investigated the intra- and inter-individual variability of autophagy and apoptosis activities in women during pregnancy. The aim of this project is to study autophagy and apoptosis activities specifically in women developing a placental vascular complication during pregnancy.

Detailed description: Pregnancy increases the risk of thrombosis. Diseases mediated by the placenta are a risk factor for cardiovascular pathologies. They are responsible for significant maternal-fetal morbidity and mortality. Understanding and exploring the cellular and molecular mechanisms of dysfunctions at the vascular-placental interface could provide arguments for understanding systemic vascular risk, characterizing it and ultimately screening for it on the basis of new markers, thus paving the way for targeted preventive management, feeding into the general principle of precision medicine.

Autophagy enables cell development, differentiation and survival, but if deregulated, it could be the starting point for cell death by apoptosis or necrosis, and promote the development of complications.

The pathophysiological mechanisms involved in trophoblast apoptosis are incompletely described. A deregulation of the trophoblast proliferation/cell death balance could be at the origin of placental pathologies. The regulation of autophagy and autophagy-dependent events during pregnancy have not been fully identified.

We hypothesize that there is an intratrophoblastic dialogue between autophagy and apoptosis mechanisms, with the promotion of one partially inhibiting the other. The increase in trophoblastic autophagy during pregnancy could thus constitute an anti-apoptosis defense phenomenon, whose depletion would lead to cellular apoptosis and pathogenic consequences when it devastates the syncytiotrophoblast.

This project follows on from the GrossAuTop-1 study, which investigated the intra- and inter-individual variability of autophagy and apoptosis activities in women during pregnancy: the inclusions corresponded to all-pregnant women, the majority of whom developed a normal pregnancy. The aim of this project is to study autophagy and apoptosis activities specifically in women developing a placental vascular complication during pregnancy.

Eligibility criteria: Inclusion Criteria:

* Pregnant women developing a placental vascular complication (preeclampsia and/or intrauterine growth retardation), hospitalized and delivering at Nîmes University Hospital.
* Pregnant woman with free and informed consent.
* Pregnant woman affiliated with and/or benefiting from a health insurance scheme.

Exclusion criteria:

* Multiple pregnancy.
* Presence of hypertension and/or proteinuria prior to pregnancy.
* Participant in an interventional drug study.
* Persons in a period of exclusion determined by another study.
* Persons under court protection, guardianship or curatorship.
* Persons unable to give consent.
* Persons for whom it is impossible to give informed information.

Primary outcomes:
measure: Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
timeFrame: Baseline
measure: Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
timeFrame: Month 1
measure: Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
timeFrame: Month 2
measure: Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
timeFrame: Month 3
measure: Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
timeFrame: Month 4
measure: Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
timeFrame: At delivery
Secondary outcomes:
measure: Apoptosis activity
timeFrame: Baseline
measure: A. Apoptosis activity
timeFrame: Month 1
measure: A. Apoptosis activity
timeFrame: Month 2
measure: A. Apoptosis activity
timeFrame: Month 3
measure: A. Apoptosis activity
timeFrame: Month 4
measure: A. Apoptosis activity
timeFrame: At delivery
measure: B. Autophagy/apoptosis balance
timeFrame: Baseline
measure: B. Autophagy/apoptosis balance
timeFrame: Month 1
measure: B. Autophagy/apoptosis balance
timeFrame: Month 2
measure: B. Autophagy/apoptosis balance
timeFrame: Month 3
measure: B. Autophagy/apoptosis balance
timeFrame: Month 4
measure: B. Autophagy/apoptosis balance
timeFrame: At delivery
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein
timeFrame: Baseline
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein
timeFrame: Month 1
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein
timeFrame: Month 2
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein
timeFrame: Month 3
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein
timeFrame: Month 4
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein
timeFrame: At delivery
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V
timeFrame: Baseline
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V
timeFrame: Month 1
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V
timeFrame: Month 2
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V
timeFrame: Month 3
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V
timeFrame: Month 4
measure: C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V
timeFrame: At delivery
measure: D. Concentration of circulating Placental Growth Factor
timeFrame: Baseline
measure: D. Concentration of circulating Placental Growth Factor
timeFrame: Month 1
measure: D. Concentration of circulating Placental Growth Factor
timeFrame: Month 2
measure: D. Concentration of circulating Placental Growth Factor
timeFrame: Month 3
measure: D. Concentration of circulating Placental Growth Factor
timeFrame: Month 4
measure: D. Concentration of circulating Placental Growth Factor
timeFrame: At delivery
measure: D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1
timeFrame: Baseline
measure: D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1
timeFrame: Month 1
measure: D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1
timeFrame: Month 2
measure: D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1
timeFrame: Month 3
measure: D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1
timeFrame: Month 4
measure: D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1
timeFrame: At delivery
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria
timeFrame: Baseline
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria
timeFrame: Month 1
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria
timeFrame: Month 2
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria
timeFrame: Month 3
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria
timeFrame: Month 4
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria
timeFrame: At delivery
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria
timeFrame: Baseline
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria
timeFrame: Month 1
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria
timeFrame: Month 2
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria
timeFrame: Month 3
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria
timeFrame: Month 4
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria
timeFrame: At delivery
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein
timeFrame: Baseline
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein
timeFrame: Month 1
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein
timeFrame: Month 2
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein
timeFrame: Month 3
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein
timeFrame: Month 4
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein
timeFrame: At delivery
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen
timeFrame: Baseline
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen
timeFrame: Month 1
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen
timeFrame: Month 2
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen
timeFrame: Month 3
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen
timeFrame: Month 4
measure: E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen
timeFrame: At delivery
measure: E. Coagulation parameters : activated partial thromboplastin time
timeFrame: Baseline
measure: E. Coagulation parameters : activated partial thromboplastin time
timeFrame: Month 1
measure: E. Coagulation parameters : activated partial thromboplastin time
timeFrame: Month 2
measure: E. Coagulation parameters : activated partial thromboplastin time
timeFrame: Month 3
measure: E. Coagulation parameters : activated partial thromboplastin time
timeFrame: Month 4
measure: E. Coagulation parameters : activated partial thromboplastin time
timeFrame: At delivery
measure: E. Coagulation parameters : Prothrombin time
timeFrame: Baseline
measure: E. Coagulation parameters : Prothrombin time
timeFrame: Month 1
measure: E. Coagulation parameters : Prothrombin time
timeFrame: Month 2
measure: E. Coagulation parameters : Prothrombin time
timeFrame: Month 3
measure: E. Coagulation parameters : Prothrombin time
timeFrame: Month 4
measure: E. Coagulation parameters : Prothrombin time
timeFrame: At delivery
measure: E. Coagulation parameters : Fibrinogen
timeFrame: Baseline
measure: E. Coagulation parameters : Fibrinogen
timeFrame: Month 1
measure: E. Coagulation parameters : Fibrinogen
timeFrame: Month 2
measure: E. Coagulation parameters : Fibrinogen
timeFrame: Month 3
measure: E. Coagulation parameters : Fibrinogen
timeFrame: Month 4
measure: E. Coagulation parameters : Fibrinogen
timeFrame: At delivery
measure: E. Coagulation parameters : D-dimers
timeFrame: Baseline
measure: E. Coagulation parameters : D-dimers
timeFrame: Month 1
measure: E. Coagulation parameters : D-dimers
timeFrame: Month 2
measure: E. Coagulation parameters : D-dimers
timeFrame: Month 3
measure: E. Coagulation parameters : D-dimers
timeFrame: Month 4
measure: E. Coagulation parameters : D-dimers
timeFrame: At delivery
measure: E. Coagulation parameters : Fibrin monomers
timeFrame: Baseline
measure: E. Coagulation parameters : Fibrin monomers
timeFrame: Month 1
measure: E. Coagulation parameters : Fibrin monomers
timeFrame: Month 2
measure: E. Coagulation parameters : Fibrin monomers
timeFrame: Month 3
measure: E. Coagulation parameters : Fibrin monomers
timeFrame: Month 4
measure: E. Coagulation parameters : Fibrin monomers
timeFrame: At delivery
measure: E. Coagulation parameters : Thrombin generation time
timeFrame: Baseline
measure: E. Coagulation parameters : Thrombin generation time
timeFrame: Month 1
measure: E. Coagulation parameters : Thrombin generation time
timeFrame: Month 2
measure: E. Coagulation parameters : Thrombin generation time
timeFrame: Month 3
measure: E. Coagulation parameters : Thrombin generation time
timeFrame: Month 4
measure: E. Coagulation parameters : Thrombin generation time
timeFrame: At delivery
measure: Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils
timeFrame: Baseline
measure: Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils
timeFrame: Month 1
measure: Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils
timeFrame: Month 2
measure: Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils
timeFrame: Month 3
measure: Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils
timeFrame: Month 4
measure: Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils
timeFrame: At delivery
measure: Complete Blood Count : Red blood cells
timeFrame: Baseline
measure: Complete Blood Count : Red blood cells
timeFrame: Month 1
measure: Complete Blood Count : Red blood cells
timeFrame: Month 2
measure: Complete Blood Count : Red blood cells
timeFrame: Month 3
measure: Complete Blood Count : Red blood cells
timeFrame: Month 4
measure: Complete Blood Count : Red blood cells
timeFrame: At delivery
measure: Complete Blood Count : Hemoglobin
timeFrame: Baseline
measure: Complete Blood Count : Hemoglobin
timeFrame: Month 1
measure: Complete Blood Count : Hemoglobin
timeFrame: Month 2
measure: Complete Blood Count : Hemoglobin
timeFrame: Month 3
measure: Complete Blood Count : Hemoglobin
timeFrame: Month 4
measure: Complete Blood Count : Hemoglobin
timeFrame: At delivery
measure: Complete Blood Count : Platelets
timeFrame: Baseline
measure: Complete Blood Count : Platelets
timeFrame: Month 1
measure: Complete Blood Count : Platelets
timeFrame: Month 2
measure: Complete Blood Count : Platelets
timeFrame: Month 3
measure: Complete Blood Count : Platelets
timeFrame: Month 4
measure: Complete Blood Count : Platelets
timeFrame: At delivery
measure: Complete Blood Count : Hematocrit
timeFrame: Baseline
measure: Complete Blood Count : Hematocrit
timeFrame: Month 1
measure: Complete Blood Count : Hematocrit
timeFrame: Month 2
measure: Complete Blood Count : Hematocrit
timeFrame: Month 3
measure: Complete Blood Count : Hematocrit
timeFrame: Month 4
measure: Complete Blood Count : Hematocrit
timeFrame: At delivery
measure: Complete Blood Count : Mean Corpuscular Volume
timeFrame: Baseline
measure: Complete Blood Count : Mean Corpuscular Volume
timeFrame: Month 1
measure: Complete Blood Count : Mean Corpuscular Volume
timeFrame: Month 2
measure: Complete Blood Count : Mean Corpuscular Volume
timeFrame: Month 3
measure: Complete Blood Count : Mean Corpuscular Volume
timeFrame: Month 4
measure: Complete Blood Count : Mean Corpuscular Volume
timeFrame: At delivery
measure: Complete Blood Count : Mean Corpuscular Hemoglobin
timeFrame: Baseline
measure: Complete Blood Count : Mean Corpuscular Hemoglobin
timeFrame: Month 1
measure: Complete Blood Count : Mean Corpuscular Hemoglobin
timeFrame: Month 2
measure: Complete Blood Count : Mean Corpuscular Hemoglobin
timeFrame: Month 3
measure: Complete Blood Count : Mean Corpuscular Hemoglobin
timeFrame: Month 4
measure: Complete Blood Count : Mean Corpuscular Hemoglobin Concentration
timeFrame: Baseline
measure: Complete Blood Count : Mean Corpuscular Hemoglobin Concentration
timeFrame: Month 1
measure: Complete Blood Count : Mean Corpuscular Hemoglobin Concentration
timeFrame: Month 2
measure: Complete Blood Count : Mean Corpuscular Hemoglobin Concentration
timeFrame: Month 3
measure: Complete Blood Count : Mean Corpuscular Hemoglobin Concentration
timeFrame: At delivery
measure: Ferritin
timeFrame: Baseline
measure: Ferritin
timeFrame: Month 1
measure: Ferritin
timeFrame: Month 2
measure: Ferritin
timeFrame: Month 3
measure: Ferritin
timeFrame: Month 4
measure: Ferritin
timeFrame: At delivery
measure: F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia
timeFrame: Baseline
measure: F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia
timeFrame: Month 1
measure: F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia
timeFrame: Month 2
measure: F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia
timeFrame: Month 3
measure: F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia
timeFrame: Month 4
measure: F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia
timeFrame: At delivery
measure: F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia
timeFrame: Baseline
measure: F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia
timeFrame: Month 1
measure: F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia
timeFrame: Month 2
measure: F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia
timeFrame: Month 3
measure: F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia
timeFrame: Month 4
measure: F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia
timeFrame: At delivery
measure: Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance
timeFrame: Baseline
measure: Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance
timeFrame: Month 1
measure: Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance
timeFrame: Month 2
measure: Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance
timeFrame: Month 3
measure: Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance
timeFrame: Month 4
measure: Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance
timeFrame: At delivery
measure: H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.
timeFrame: Baseline
measure: H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.
timeFrame: Month 1
measure: H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.
timeFrame: Month 2
measure: H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.
timeFrame: Month 3
measure: H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.
timeFrame: Month 4
measure: H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.
timeFrame: At delivery
Other outcomes:
measure: I. Constitution of a Biobank
timeFrame: Baseline
Locations:
city: Nîmes
country: France
facility: Nimes University Hospital
Study officials:
affiliation: Nîmes University Hospital
name: Marie PORTES, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Nîmes University Hospital
name: Mathieu FORTIER, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Nîmes University Hospital
name: Jean-Christophe GRIS, Pr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Nîmes University Hospital
name: Eve MOUSTY, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Nîmes University Hospital
name: Vincent LETOUZEY, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Nîmes University Hospital
name: Stéphanie HUBERLANT, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Nîmes University Hospital
name: Chloé BOURGUIGNON, Dr.
role: PRINCIPAL_INVESTIGATOR
References: