Free DNA and Nucleosome Concentrations in Pathological Pregnancies

Completed

• Conditions: Pregnancy; Eclampsia; Venous Thrombosis; Pulmonary Embolism; Hypertension, Pregnancy-Induced; HELLP Syndrome; Pre-Eclampsia; Fetal Death; Placental Insufficiency
• Interventions: Biological: Bloodwork, baseline; Biological: Blood work, Months 1 & 2; Biological: Bloodwork, Months -1 to -6

• Registration Number: NCT01736826
• Lead Sponsor: Centre Hospitalier Universitaire de Nīmes

Brief 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).

Detailed 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.

Study Timeline

• Study First Submitted: 2012-11-27
• Study First Submitted QC: 2012-11-27
• Study First Posted: 2012-11-29
• Study Start: 2015-06
• Primary Completion: 2018-12-17
• Study Completion: 2018-12-17
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-10
• Last Update Posted: 2019-01-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 137

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group T1x: 15 Healthy volunteers	Blood work, Months 1 & 2	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
Group P: pregnancy w/complications	Bloodwork, baseline	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
Group T1: Healthy volunteers	Bloodwork, baseline	Healthy volunteers with no history of chronic or neoplastic disease. 30 healthy volunteers will be included. Interventions to be administered: Bloodwork, baseline
Group T2: Pregnancy, no complications	Bloodwork, baseline	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
Group T2x: 15 Pregnancy, no complications	Bloodwork, baseline	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
Group T2x: 15 Pregnancy, no complications	Bloodwork, Months -1 to -6	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
Group T1x: 15 Healthy volunteers	Bloodwork, baseline	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

Primary Outcome Measures

Name	Time	Method
Total plasma concentration of nucleosomes (AU)	Base line (day 0)	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
Total plasma concentration of free DNA (ng/ml)	Base line (day 0)	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.

Secondary Outcome Measures

Name	Time	Method
Fibrinogen (g/l)	-6 months	For group T2x only.
Monocytes (g/l)	-6 months	For group T2x only.
Lymphocytes (g/l)	-6 months	For group T2x only.
Hemoglobin (g/l)	-6 months	For group T2x only
Platelets (g/l)	-6 months	For group T2x only
Mean corpuscular volume (fL)	-6 months	For group T2x only
Leukocytes (g/l)	-6 months	For group T2x only
Polynuclear neutrophils(g/l)	-6 months	For group T2x only
Total plasma concentration of nucleosomes (AU)	-6 months	For group T2x only.
Mean corpuscular hemoglobin (pg/GR)	-6 months	For group T2x only.
Trophoblast microparticles (%)	-6 months	For group T2x only.
Total plasma concentration of free DNA (ng/ml)	-6 months	For group T2x only.
Polynuclear eosinophils (g/l)	-6 months	For group T2x only.
Polynuclear basophils (g/l)	-6 months	For group T2x only.
D-dimers (ng/ml)	-6 months	For group T2x only.
Fibrin monomers (ng/ml)	-6 months	For group T2x only.
Angiogenic marker CD146 (ng/ml)	-6 months	For group T2x only.

Trial Locations

Locations (1)

CHU de Nîmes - Hôpital Universitaire Carémeau; 🇫🇷 Nîmes Cedex 9, France