Autophagy/Apoptosis Balance During Pregnancy (GROSSAUTOP)

The object of this study is to assess the intra- and inter-individual variability of apoptosis and autophagy activities in women during pregnancy: 1 / in women with a normal pregnancy and 2 / in pregnant women particularly at risk of complications.

The study investigators hypothesize that there would be an intra-trophoblastic dialogue between the mechanisms of autophagy and apoptosis, the promotion of one partially inhibiting the other. The increase in trophoblastic autophagy during pregnancy could thus constitute an anti-apoptosis defense phenomenon, the exhaustion of which would lead to cellular apoptosis and to pathogenic consequences when it devastates the syncytiotrophoblast.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy Related
• Intervention / Treatment: Other: Blood test

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Sylvie Bouvier; Phone Number: 04.66.68.32.11; Email: sylvie.bouvier@chu-nimes.fr

Study Locations

• France
  • Nîmes, France
    • Recruiting
    • CHU de Nimes
    • Sub-Investigator: Jean-Christophe Gris
    • Principal Investigator: Sylvie Bouvier
    • Sub-Investigator: Eve Mousty
    • Sub-Investigator: Hélène Martin
    • Sub-Investigator: Marie Porte
    • Sub-Investigator: Erick Mercier
    • Sub-Investigator: Eva Nouvellon
    • Contact: Anissa Megzari; Phone Number: 04.66.68.42.36; Email: drc@chu-nimes.fr
    • Sub-Investigator: Vincent Letouzey
    • Sub-Investigator: Marine Commissaire

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All pregnant women followed at the Nîmes University Hospital for their pregnancy. Patients will be recruited among those consulting hospital gynecologists from the 3rd month of pregnancy but also through the circuit of specific gynecology-obstetrics consultations receiving in particular women with a history and / or risk factors for pathological pregnancy

Description

Inclusion Criteria:

• Patients followed at the CHU Nîmes prior to 33 weeks gestation who give birth at the hospital
• The patient must have given their free and informed consent and signed the consent form
• The patient must be a member or beneficiary of a health insurance plan

Exclusion Criteria:

• The subject is participating in a category 1 interventional study associated with a medication, or is in a period of exclusion determined by a previous study
• The subject refuses to sign the consent
• It is impossible to give the subject informed information
• The patient is under safeguard of justice or state guardianship
• Multiple pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; without medical history or risk factors, with a normal pregnancy	Other: Blood test; Blood samples taken to test levels of autophagy and apoptosis
Group B; without medical history or risk factors, developing a pregnancy complication	Other: Blood test; Blood samples taken to test levels of autophagy and apoptosis
Group C; with risk of complication, having a normal pregnancy	Other: Blood test; Blood samples taken to test levels of autophagy and apoptosis
Group D; with a risk of complication, developing a pregnancy complication	Other: Blood test; Blood samples taken to test levels of autophagy and apoptosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Potential autophagy induction activity in all groups	Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Day 0
Potential autophagy induction activity in all groups	Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 1
Potential autophagy induction activity in all groups	Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 2
Potential autophagy induction activity in all groups	Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 3
Potential autophagy induction activity in all groups	Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 4
Potential autophagy induction activity in all groups	Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 5
Potential autophagy induction activity in all groups	Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Delivery plus or minus 2 weeks (Month 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of autophagy inhibition per patient in all groups	Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Day 0
Type of autophagy inhibition per patient in all groups	Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 1
Type of autophagy inhibition per patient in all groups	Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 2
Type of autophagy inhibition per patient in all groups	Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 3
Type of autophagy inhibition per patient in all groups	Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 4
Type of autophagy inhibition per patient in all groups	Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 5
Type of autophagy inhibition per patient in all groups	Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Delivery plus or minus 2 weeks (Month 6)
Potential apoptosis induction activity in all groups	% cells positive for Annexin V	Day 0
Potential apoptosis induction activity in all groups	% cells positive for Annexin V	Month 1
Potential apoptosis induction activity in all groups	% cells positive for Annexin V	Month 2
Potential apoptosis induction activity in all groups	% cells positive for Annexin V	Month 3
Potential apoptosis induction activity in all groups	% cells positive for Annexin V	Month 4
Potential apoptosis induction activity in all groups	% cells positive for Annexin V	Month 5
Potential apoptosis induction activity in all groups	% cells positive for Annexin V	Delivery plus or minus 2 weeks (Month 6)
Inter- and intra-individual apoptosis/autophagy ratio in all groups		Day 0
Inter- and intra-individual apoptosis/autophagy ratio in all groups		Month 1
Inter- and intra-individual apoptosis/autophagy ratio in all groups		Month 2
Inter- and intra-individual apoptosis/autophagy ratio in all groups		Month 3
Inter- and intra-individual apoptosis/autophagy ratio in all groups		Month 4
Inter- and intra-individual apoptosis/autophagy ratio in all groups		Month 5
Inter- and intra-individual apoptosis/autophagy ratio in all groups		Delivery plus or minus 2 weeks (Month 6)
Autophagy kinetics between groups	measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Day 0
Autophagy kinetics between groups	measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 1
Autophagy kinetics between groups	measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 2
Autophagy kinetics between groups	measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 3
Autophagy kinetics between groups	measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 4
Autophagy kinetics between groups	measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Month 5
Autophagy kinetics between groups	measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio	Delivery plus or minus 2 weeks (Month 6)
Apoptosis kinetics between groups	measured by % cells positive for Annexin V	Day 0
Apoptosis kinetics between groups	measured by % cells positive for Annexin V	Month 1
Apoptosis kinetics between groups	measured by % cells positive for Annexin V	Month 2
Apoptosis kinetics between groups	measured by % cells positive for Annexin V	Month 3
Apoptosis kinetics between groups	measured by % cells positive for Annexin V	Month 4
Apoptosis kinetics between groups	measured by % cells positive for Annexin V	Month 5
Apoptosis kinetics between groups	measured by % cells positive for Annexin V	Delivery plus or minus 2 weeks (Month 6)
Placental Growth Factor in each group	pg/ml measured by ELISA	Day 0
Placental Growth Factor in each group	pg/ml measured by ELISA	Month 1
Placental Growth Factor in each group	pg/ml measured by ELISA	Month 2
Placental Growth Factor in each group	pg/ml measured by ELISA	Month 3
Placental Growth Factor in each group	pg/ml measured by ELISA	Month 4
Placental Growth Factor in each group	pg/ml measured by ELISA	Month 5
Placental Growth Factor in each group	pg/ml measured by ELISA	Delivery plus or minus 2 weeks (Month 6)
Soluble fms-like tyrosine kinase-1	pg/ml measured by ELISA	Day 0
Soluble fms-like tyrosine kinase-1	pg/ml measured by ELISA	Month 1
Soluble fms-like tyrosine kinase-1	pg/ml measured by ELISA	Month 2
Soluble fms-like tyrosine kinase-1	pg/ml measured by ELISA	Month 3
Soluble fms-like tyrosine kinase-1	pg/ml measured by ELISA	Month 4
Soluble fms-like tyrosine kinase-1	pg/ml measured by ELISA	Month 5
Soluble fms-like tyrosine kinase-1	pg/ml measured by ELISA	Delivery plus or minus 2 weeks (Month 6)
Constitutive thrombophilia	presence/absence of the prothrombin gene or factor V Leiden mutation, protein S, C or antithrombin deficiency	Day 0
Acquired thrombophilia	Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid).	Day 0
Acquired thrombophilia	Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid).	Month 1
Acquired thrombophilia	Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid).	Month 2
Acquired thrombophilia	Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid).	Month 3
Acquired thrombophilia	Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid).	Month 4
Acquired thrombophilia	Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid).	Month 5
Acquired thrombophilia	Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid).	Delivery plus or minus 2 weeks (Month 6)
Whole blood count		Day 0
Whole blood count		Month 1
Whole blood count		Month 2
Whole blood count		Month 3
Whole blood count		Month 4
Whole blood count		Month 5
Whole blood count		Delivery plus or minus 2 weeks (Month 6)
Renal function	creatinemia, proteinuria / creatinuria ratio	Day 0
Renal function	creatinemia, proteinuria / creatinuria ratio	Month 1
Renal function	creatinemia, proteinuria / creatinuria ratio	Month 2
Renal function	creatinemia, proteinuria / creatinuria ratio	Month 3
Renal function	creatinemia, proteinuria / creatinuria ratio	Month 4
Renal function	creatinemia, proteinuria / creatinuria ratio	Month 5
Renal function	creatinemia, proteinuria / creatinuria ratio	Delivery plus or minus 2 weeks (Month 6)
Fibrin levels	D dimers and fibrin monomers	Day 0
Fibrin levels	D dimers and fibrin monomers	Month 1
Fibrin levels	D dimers and fibrin monomers	Month 2
Fibrin levels	D dimers and fibrin monomers	Month 3
Fibrin levels	D dimers and fibrin monomers	Month 4
Fibrin levels	D dimers and fibrin monomers	Month 5
Fibrin levels	D dimers and fibrin monomers	Delivery plus or minus 2 weeks (Month 6)
Inflammation	C-reactive protein level	Day 0
Inflammation	C-reactive protein level	Month 1
Inflammation	C-reactive protein level	Month 2
Inflammation	C-reactive protein level	Month 3
Inflammation	C-reactive protein level	Month 4
Inflammation	C-reactive protein level	Month 5
Inflammation	C-reactive protein level	Delivery plus or minus 2 weeks (Month 6)
Activated partial thromboplastin time	seconds	Day 0
Activated partial thromboplastin time	seconds	Month 1
Activated partial thromboplastin time	seconds	Month 2
Activated partial thromboplastin time	seconds	Month 3
Activated partial thromboplastin time	seconds	Month 4
Activated partial thromboplastin time	seconds	Month 5
Activated partial thromboplastin time	seconds	Delivery plus or minus 2 weeks (Month 6)
Prothrombin time	seconds	Day 0
Prothrombin time	seconds	Month 1
Prothrombin time	seconds	Month 2
Prothrombin time	seconds	Month 3
Prothrombin time	seconds	Month 4
Prothrombin time	seconds	Month 5
Prothrombin time	seconds	Delivery plus or minus 2 weeks (Month 6)
Fibrinogen level	g/L	Day 0
Fibrinogen level	g/L	Month 1
Fibrinogen level	g/L	Month 2
Fibrinogen level	g/L	Month 3
Fibrinogen level	g/L	Month 4
Fibrinogen level	g/L	Month 5
Fibrinogen level	g/L	Delivery plus or minus 2 weeks (Month 6)
Thrombin generation time	seconds	Month 1
Thrombin generation time	seconds	Month 2
Thrombin generation time	seconds	Month 3
Thrombin generation time	seconds	Month 4
Thrombin generation time	seconds	Month 5
Thrombin generation time	seconds	Delivery plus or minus 2 weeks (Month 6)
Thrombin generation time	seconds	Day 0
fetal haemoglobin	g/L	Month 1
fetal haemoglobin	g/L	Month 2
fetal haemoglobin	g/L	Month 3
fetal haemoglobin	g/L	Month 4
fetal haemoglobin	g/L	Month 5
fetal haemoglobin	g/L	Delivery plus or minus 2 weeks (Month 6)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Sylvie Bouvier, CHU Nimes

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 19, 2020
• First Posted (Actual): June 23, 2020

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Autophagy; Apoptosis
• Other Study ID Numbers: NIMAO/2019-01/SB-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No