Free DNA and Nucleosome Concentrations in Pathological Pregnancies

Centre Hospitalier Universitaire de Nīmes

Status: Completed

Conditions: Pre-Eclampsia; Pulmonary Embolism; Hypertension, Pregnancy-Induced; HELLP Syndrome; Eclampsia; Fetal Death; Venous Thrombosis; Placental Insufficiency; Pregnancy

Treatments: Biological: Bloodwork, Months -1 to -6; Biological: Bloodwork, baseline; Biological: Blood work, Months 1 & 2

Study type: Observational

Funder types: Other

Identifiers

NCT01736826

2014-A01120-47 (Other Identifier)

LOCAL/2012/SB-01

Details and patient eligibility

About

The primary objective of this study is to demonstrate that plasma concentrations of nucleosomes and free DNA differ between three groups:

1. pregnant patients with complications typical of placental insufficiency or venous thrombosis (group P),
2. healthy women (Group T1) and
3. healthy pregnant women (Group T2).

Full description

Our secondary objectives include the following:

1. To describe, in 15 healthy, non-pregnant women changes in plasma concentrations of nucleosomes and free DNA over 3 months.
2. To describe, in 15 pregnant women (without complications), changes in plasma concentrations of nucleosomes and free DNA over the last 7 months of pregnancy
3. To show that plasma concentrations of nucleosomes and free DNA, in patients with complicated pregnancies differ according to the nature of the complication
4. To show that a relationship exists between the concentrations of nucleosomes, free DNA, and total granulocyte microparticles (and trophoblast particles for pregnant women)
5. To evaluate the relationship between nucleosome concentrations, free DNA concentrations and circulating leukocyte populations
6. To evaluate the relationship between nucleosome concentrations, free DNA concentrations and hemostasis markers
7. To describe changes in hemostasis markers throughout pregnancy
8. To evaluate the relationship between nucleosome concentrations, free DNA concentrations and the angiogenic marker CD146
9. To add to the Nîmes University Hospital biological collections.

Enrollment: 137 patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for all patients:

• The patient must have given her informed and signed consent
• The patient must be insured or beneficiary of a health insurance plan

Inclusion Criteria for patients in group P:

• The patient is pregnant and has complications typical of placental vascular disease (preeclampsia, eclampsia, HELLP syndrome, retro-placental hematoma, in utero fetal death) or venous thromboembolism (deep vein thrombosis, pulmonary embolism)

Inclusion Criteria for patients in group T1:

• The patient is available for 3 months of follow-up
• The patient is a non-pregnant healthy volunteer
• No identifiable chronic pathologies
• No history of neoplastic disease
• No history of chronic infectious disease
• No acute disease (such as benign infection), now or within the past two weeks

Inclusion Criteria for patients in group T2:

• The patient is available for 7 months of follow-up
• The patient is pregnant, with no identifiable pregnancy complications
• No identifiable chronic pathologies
• No history of neoplastic disease
• No history of chronic infectious disease
• No acute disease (such as benign infection), now or within the past two weeks

Exclusion Criteria for all patients:

• The patient is participating in another study (with the exception of the following studies: PAPILLO-PMA (2013-A00538-37), ElastoMAP (2013-A01148-37), ElastoDéclenche (2014-A00828-39), LXRs (2009-A00968-49), Bakri (2013-A00914-41), OASIS 2 (2013-A00022-43)).
• The patient is in an exclusion period determined by a previous study
• The patient is under judicial protection, under tutorship or curatorship
• The patient refuses to sign the consent
• It is impossible to correctly inform the patient
• The patient cannot read French
• The patient is receiving hormonal ovarian stimulation in the context of medically assisted procreation
• Impossible to perform venipuncture under good conditions
• New complication or pathology during the study (except for pregnancy complications in group P)

Exclusion Criteria for group P:

• Twin or multiple pregnancy
• The patient is participating in another study (with the exception of those mentioned in the exclusion criteria for all patients and the DG Postpartum study (2013-A00277-38)

Exclusion Criteria for group T1:

• The patient is pregnant
• The patient is breast feeding
• The patient has given birth within the last 3 months
• Known history of chronic disease
• History of treated neoplastic disease
• Acute disease within the past two weeks (includes benign disease)

Exclusion Criteria for group T2:

• Pregnancy with complications
• Known history of chronic disease
• History of treated neoplastic disease
• Acute disease within the past two weeks (includes benign disease)
• Twin or multiple pregnancy

Trial design

137 participants in 5 patient groups

Group P: pregnancy w/complications

Description:

The patient is pregnant and has complications typical of placental vascular disease (preeclampsia, eclampsia, HELLP syndrome, retro-placental hematoma, in utero fetal death) or venous thromboembolism (deep vein thrombosis, pulmonary embolism). 100 patients will be included. Interventions to be administered: Bloodwork, baseline

Treatment:

Biological: Bloodwork, baseline

Group T1: Healthy volunteers

Description:

Healthy volunteers with no history of chronic or neoplastic disease. 30 healthy volunteers will be included. Interventions to be administered: Bloodwork, baseline

Treatment:

Biological: Bloodwork, baseline

Group T2: Pregnancy, no complications

Description:

Pregnant patients with no identifiable pregnancy complications, and no history of chronic or neoplastic disease. 50 pregnant volunteers will be included. Interventions to be administered: Bloodwork, baseline

Treatment:

Biological: Bloodwork, baseline

Group T1x: 15 Healthy volunteers

Description:

15 Healthy volunteers selected from group T1 (the first 15). These patients will have 2 additional months of follow up. Interventions to be administered: Blood work, Months 1 \& 2

Treatment:

Biological: Blood work, Months 1 & 2

Biological: Bloodwork, baseline

Group T2x: 15 Pregnancy, no complications

Description:

15 patients selected from group T2 (the first 15); these patients will have 7 months of follow up during pregnancy. Interventions to be administered: Bloodwork, Months -1 to -6

Treatment:

Biological: Bloodwork, baseline

Biological: Bloodwork, Months -1 to -6