Free DNA and Nucleosome Concentrations in Pathological Pregnancies

Pregnancy Clinical Trial

Official title:

Comparative Study of Plasma Free DNA and Nucleosome Concentrations: Pathological Versus Normal Pregnancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01736826
• Other study ID #: LOCAL/2012/SB-01
• Secondary ID: 2014-A01120-47
• Status: Completed
• Start date: June 2015
• Est. completion date: December 17, 2018

Study information

• Verified date: January 2019
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: December 17, 2018
• Est. primary completion date: December 17, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• Bloodwork, baseline
36 ml of blood are drawn at baseline (last month of pregnancy for groups P and T2, inclusion for group T1) in order to quantify the following: plasma free DNA concentration, plasma nucleosome concentration, hemoglobin, platelets, leukocytes, polynuclear neutrophils, mean corpuscular volume, monocytes, mean corpuscular hemoglobin, lymphocytes, polynuclear eosinophils, polynuclear basophils, D-Dimers, Fibrin monomers, Trophoblast microparticles, Angiogenic marker CD146.
• Blood work, Months 1 & 2
36 ml of blood are drawn at 1 & 2 months after inclusion in order to quantify the following: plasma free DNA concentration, plasma nucleosome concentration, hemoglobin, platelets, leukocytes, polynuclear neutrophils, mean corpuscular volume, monocytes, mean corpuscular hemoglobin, lymphocytes, polynuclear eosinophils, polynuclear basophils, D-Dimers, Fibrin monomers, Trophoblast microparticles, Angiogenic marker CD146.
• Bloodwork, Months -1 to -6
36 ml of blood are drawn at the third, fourth, fifth, sixth, seventh and eight months of normal pregnancy (corresponding to months -1 to -6 before comparative baseline; this group is included in the study early during pregnancy)in order to quantify the following: plasma free DNA concentration, plasma nucleosome concentration, hemoglobin, platelets, leukocytes, polynuclear neutrophils, mean corpuscular volume, monocytes, mean corpuscular hemoglobin, lymphocytes, polynuclear eosinophils, polynuclear basophils, D-Dimers, Fibrin monomers, Trophoblast microparticles, Angiogenic marker CD146.

Locations

Country	Name	City	State
France	CHU de Nîmes - Hôpital Universitaire Carémeau	Nîmes Cedex 9

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total plasma concentration of free DNA (ng/ml)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	Base line (day 0)
Primary	Total plasma concentration of nucleosomes (AU)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth	Base line (day 0)
Secondary	Hemoglobin (g/l)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Platelets (g/l)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Leukocytes (g/l)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Polynuclear neutrophils(g/l)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Mean corpuscular volume (fL)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Monocytes (g/l)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Mean corpuscular hemoglobin (pg/GR)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Lymphocytes (g/l)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Polynuclear eosinophils (g/l)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Polynuclear basophils (g/l)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	D-dimers (ng/ml)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Fibrin monomers (ng/ml)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Trophoblast microparticles (%)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Angiogenic marker CD146 (ng/ml)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	baseline (day 0)
Secondary	Hemoglobin (g/l)	For group T1x only	1 month
Secondary	Platelets (g/l)	For group T1x only	1 month
Secondary	Leukocytes (g/l)	For group T1x only	1 month
Secondary	Polynuclear neutrophils(g/l)	For group T1x only	1 month
Secondary	Mean corpuscular volume (fL)	For group T1x only	1 month
Secondary	Monocytes (g/l)	For group T1x only	1 month
Secondary	Mean corpuscular hemoglobin (pg/GR)	For group T1x only	1 month
Secondary	Lymphocytes (g/l)	For group T1x only	1 month
Secondary	Polynuclear eosinophils (g/l)	For group T1x only	1 month
Secondary	Polynuclear basophils (g/l)	For group T1x only	1 month
Secondary	D-dimers (ng/ml)	For group T1x only	1 month
Secondary	Fibrin monomers (ng/ml)	For group T1x only	1 month
Secondary	Trophoblast microparticles (%)	For group T1x only	1 month
Secondary	Angiogenic marker CD146 (ng/ml)	For group T1x only	1 month
Secondary	Total plasma concentration of free DNA (ng/ml)	For group T1x only	1 month
Secondary	Total plasma concentration of nucleosomes (AU)	For group T1x only	1 month
Secondary	Hemoglobin (g/l)	For group T1x only	2 months
Secondary	Platelets (g/l)	For group T1x only	2 months
Secondary	Leukocytes (g/l)	For group T1x only	2 months
Secondary	Polynuclear neutrophils(g/l)	For group T1x only	2 months
Secondary	Mean corpuscular volume (fL)	For group T1x only	2 months
Secondary	Monocytes (g/l)	For group T1x only	2 months
Secondary	Mean corpuscular hemoglobin (pg/GR)	For group T1x only	2 months
Secondary	Lymphocytes (g/l)	For group T1x only	2 months
Secondary	Polynuclear eosinophils (g/l)	For group T1x only	2 months
Secondary	Polynuclear basophils (g/l)	For group T1x only	2 months
Secondary	D-dimers (ng/ml)	For group T1x only	2 months
Secondary	Fibrin monomers (ng/ml)	For group T1x only	2 months
Secondary	Trophoblast microparticles (%)	For group T1x only	2 months
Secondary	Angiogenic marker CD146 (ng/ml)	For group T1x only	2 months
Secondary	Total plasma concentration of free DNA (ng/ml)	For group T1x only	2 months
Secondary	Total plasma concentration of nucleosomes (AU)	For group T1x only	2 months
Secondary	Hemoglobin (g/l)	For group T2x only	-1 months
Secondary	Hemoglobin (g/l)	For group T2x only	-2 months
Secondary	Hemoglobin (g/l)	For group T2x only	-3 months
Secondary	Hemoglobin (g/l)	For group T2x only	-4 months
Secondary	Hemoglobin (g/l)	For group T2x only	-5 months
Secondary	Hemoglobin (g/l)	For group T2x only	-6 months
Secondary	Platelets (g/l)	For group T2x only	-1 months
Secondary	Platelets (g/l)	For group T2x only	-2 months
Secondary	Platelets (g/l)	For group T2x only	-3 months
Secondary	Platelets (g/l)	For group T2x only	-4 months
Secondary	Platelets (g/l)	For group T2x only	-5 months
Secondary	Platelets (g/l)	For group T2x only	-6 months
Secondary	Leukocytes (g/l)	For group T2x only	-1 months
Secondary	Leukocytes (g/l)	For group T2x only	-2 months
Secondary	Leukocytes (g/l)	For group T2x only	-3 months
Secondary	Leukocytes (g/l)	For group T2x only	-4 months
Secondary	Leukocytes (g/l)	For group T2x only	-5 months
Secondary	Leukocytes (g/l)	For group T2x only	-6 months
Secondary	Polynuclear neutrophils(g/l)	For group T2x only	-1 months
Secondary	Polynuclear neutrophils(g/l)	For group T2x only	-2 months
Secondary	Polynuclear neutrophils(g/l)	For group T2x only	-3 months
Secondary	Polynuclear neutrophils(g/l)	For group T2x only	-4 months
Secondary	Polynuclear neutrophils(g/l)	For group T2x only	-5 months
Secondary	Polynuclear neutrophils(g/l)	For group T2x only	-6 months
Secondary	Mean corpuscular volume (fL)	For group T2x only	-1 months
Secondary	Mean corpuscular volume (fL)	For group T2x only	-2 months
Secondary	Mean corpuscular volume (fL)	For group T2x only	-3 months
Secondary	Mean corpuscular volume (fL)	For group T2x only	-4 months
Secondary	Mean corpuscular volume (fL)	For group T2x only	-5 months
Secondary	Mean corpuscular volume (fL)	For group T2x only	-6 months
Secondary	Monocytes (g/l)	For group T2x only.	-1 months
Secondary	Monocytes (g/l)	For group T2x only.	-2 months
Secondary	Monocytes (g/l)	For group T2x only.	-3 months
Secondary	Monocytes (g/l)	For group T2x only.	-4 months
Secondary	Monocytes (g/l)	For group T2x only.	-5 months
Secondary	Monocytes (g/l)	For group T2x only.	-6 months
Secondary	Mean corpuscular hemoglobin (pg/GR)	For group T2x only.	-1 months
Secondary	Mean corpuscular hemoglobin (pg/GR)	For group T2x only.	-2 months
Secondary	Mean corpuscular hemoglobin (pg/GR)	For group T2x only.	-3 months
Secondary	Mean corpuscular hemoglobin (pg/GR)	For group T2x only.	-4 months
Secondary	Mean corpuscular hemoglobin (pg/GR)	For group T2x only.	-5 months
Secondary	Mean corpuscular hemoglobin (pg/GR)	For group T2x only.	-6 months
Secondary	Lymphocytes (g/l)	For group T2x only.	-1 months
Secondary	Lymphocytes (g/l)	For group T2x only.	-2 months
Secondary	Lymphocytes (g/l)	For group T2x only.	-3 months
Secondary	Lymphocytes (g/l)	For group T2x only.	-4 months
Secondary	Lymphocytes (g/l)	For group T2x only.	-5 months
Secondary	Lymphocytes (g/l)	For group T2x only.	-6 months
Secondary	Polynuclear eosinophils (g/l)	For group T2x only.	-1 months
Secondary	Polynuclear eosinophils (g/l)	For group T2x only.	-2 months
Secondary	Polynuclear eosinophils (g/l)	For group T2x only.	-3 months
Secondary	Polynuclear eosinophils (g/l)	For group T2x only.	-4 months
Secondary	Polynuclear eosinophils (g/l)	For group T2x only.	-5 months
Secondary	Polynuclear eosinophils (g/l)	For group T2x only.	-6 months
Secondary	Polynuclear basophils (g/l)	For group T2x only.	-1 months
Secondary	Polynuclear basophils (g/l)	For group T2x only.	-2 months
Secondary	Polynuclear basophils (g/l)	For group T2x only.	-3 months
Secondary	Polynuclear basophils (g/l)	For group T2x only.	-4 months
Secondary	Polynuclear basophils (g/l)	For group T2x only.	-5 months
Secondary	Polynuclear basophils (g/l)	For group T2x only.	-6 months
Secondary	D-dimers (ng/ml)	For group T2x only.	-1 months
Secondary	D-dimers (ng/ml)	For group T2x only.	-2 months
Secondary	D-dimers (ng/ml)	For group T2x only.	-3 months
Secondary	D-dimers (ng/ml)	For group T2x only.	-4 months
Secondary	D-dimers (ng/ml)	For group T2x only.	-5 months
Secondary	D-dimers (ng/ml)	For group T2x only.	-6 months
Secondary	Fibrin monomers (ng/ml)	For group T2x only.	-1 months
Secondary	Fibrin monomers (ng/ml)	For group T2x only.	-2 months
Secondary	Fibrin monomers (ng/ml)	For group T2x only.	-3 months
Secondary	Fibrin monomers (ng/ml)	For group T2x only.	-4 months
Secondary	Fibrin monomers (ng/ml)	For group T2x only.	-5 months
Secondary	Fibrin monomers (ng/ml)	For group T2x only.	-6 months
Secondary	Trophoblast microparticles (%)	For group T2x only.	-1 months
Secondary	Trophoblast microparticles (%)	For group T2x only.	-2 months
Secondary	Trophoblast microparticles (%)	For group T2x only.	-3 months
Secondary	Trophoblast microparticles (%)	For group T2x only.	-4 months
Secondary	Trophoblast microparticles (%)	For group T2x only.	-5 months
Secondary	Trophoblast microparticles (%)	For group T2x only.	-6 months
Secondary	Angiogenic marker CD146 (ng/ml)	For group T2x only.	-1 months
Secondary	Angiogenic marker CD146 (ng/ml)	For group T2x only.	-2 months
Secondary	Angiogenic marker CD146 (ng/ml)	For group T2x only.	-3 months
Secondary	Angiogenic marker CD146 (ng/ml)	For group T2x only.	-4 months
Secondary	Angiogenic marker CD146 (ng/ml)	For group T2x only.	-5 months
Secondary	Angiogenic marker CD146 (ng/ml)	For group T2x only.	-6 months
Secondary	Total plasma concentration of nucleosomes (AU)	For group T2x only.	-1 months
Secondary	Total plasma concentration of nucleosomes (AU)	For group T2x only.	-2 months
Secondary	Total plasma concentration of nucleosomes (AU)	For group T2x only.	-3 months
Secondary	Total plasma concentration of nucleosomes (AU)	For group T2x only.	-4 months
Secondary	Total plasma concentration of nucleosomes (AU)	For group T2x only.	-5 months
Secondary	Total plasma concentration of nucleosomes (AU)	For group T2x only.	-6 months
Secondary	Total plasma concentration of free DNA (ng/ml)	For group T2x only.	-1 months
Secondary	Total plasma concentration of free DNA (ng/ml)	For group T2x only.	-2 months
Secondary	Total plasma concentration of free DNA (ng/ml)	For group T2x only.	-3 months
Secondary	Total plasma concentration of free DNA (ng/ml)	For group T2x only.	-4 months
Secondary	Total plasma concentration of free DNA (ng/ml)	For group T2x only.	-5 months
Secondary	Total plasma concentration of free DNA (ng/ml)	For group T2x only.	-6 months
Secondary	Fibrinogen (g/l)	For group P, baseline occurs within the 30 days preceding birth. For group T1, baseline = time of inclusion. For group T2, baseline occurs within the 30 days preceding birth.	Base line (day 0)
Secondary	Fibrinogen (g/l)	For group T2x only.	-1 months
Secondary	Fibrinogen (g/l)	For group T2x only.	-2 months
Secondary	Fibrinogen (g/l)	For group T2x only.	-3 months
Secondary	Fibrinogen (g/l)	For group T2x only.	-4 months
Secondary	Fibrinogen (g/l)	For group T2x only.	-5 months
Secondary	Fibrinogen (g/l)	For group T2x only.	-6 months