Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Free DNA and Nucleosome Concentrations in Pathological Pregnancies

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2014 by Centre Hospitalier Universitaire de Nīmes
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier:
NCT01736826
First received: November 27, 2012
Last updated: November 18, 2014
Last verified: November 2014
  Purpose

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).

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

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Comparative Study of Plasma Free DNA and Nucleosome Concentrations: Pathological Versus Normal Pregnancies

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nīmes:

Primary Outcome Measures:
  • Total plasma concentration of free DNA (ng/ml) [ Time Frame: Base line (day 0) ] [ Designated as safety issue: No ]
    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 nucleosomes (AU) [ Time Frame: Base line (day 0) ] [ Designated as safety issue: No ]
    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:
  • Hemoglobin (g/l) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Platelets (g/l) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Leukocytes (g/l) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Polynuclear neutrophils(g/l) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Mean corpuscular volume (µ^3) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Monocytes (g/l) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Mean corpuscular hemoglobin (pg/GR) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Lymphocytes (g/l) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Polynuclear eosinophils (g/l) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Polynuclear basophils (g/l) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • D-dimers (ng/ml) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Fibrin monomers (ng/ml) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Trophoblast microparticles (%) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Angiogenic marker CD146 (ng/ml) [ Time Frame: baseline (day 0) ] [ Designated as safety issue: No ]
    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.

  • Hemoglobin (g/l) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Platelets (g/l) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Leukocytes (g/l) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Polynuclear neutrophils(g/l) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Mean corpuscular volume (µ^3) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Monocytes (g/l) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Mean corpuscular hemoglobin (pg/GR) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Lymphocytes (g/l) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Polynuclear eosinophils (g/l) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Polynuclear basophils (g/l) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • D-dimers (ng/ml) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Fibrin monomers (ng/ml) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Trophoblast microparticles (%) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Angiogenic marker CD146 (ng/ml) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Total plasma concentration of free DNA (ng/ml) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Total plasma concentration of nucleosomes (AU) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    For group T1x only

  • Hemoglobin (g/l) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Platelets (g/l) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Leukocytes (g/l) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Polynuclear neutrophils(g/l) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Mean corpuscular volume (µ^3) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Monocytes (g/l) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Mean corpuscular hemoglobin (pg/GR) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Lymphocytes (g/l) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Polynuclear eosinophils (g/l) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Polynuclear basophils (g/l) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • D-dimers (ng/ml) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Fibrin monomers (ng/ml) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Trophoblast microparticles (%) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Angiogenic marker CD146 (ng/ml) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Total plasma concentration of free DNA (ng/ml) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Total plasma concentration of nucleosomes (AU) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    For group T1x only

  • Hemoglobin (g/l) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Hemoglobin (g/l) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Hemoglobin (g/l) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Hemoglobin (g/l) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Hemoglobin (g/l) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Hemoglobin (g/l) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Platelets (g/l) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Platelets (g/l) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Platelets (g/l) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Platelets (g/l) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Platelets (g/l) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Platelets (g/l) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Leukocytes (g/l) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Leukocytes (g/l) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Leukocytes (g/l) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Leukocytes (g/l) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Leukocytes (g/l) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Leukocytes (g/l) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Polynuclear neutrophils(g/l) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Polynuclear neutrophils(g/l) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Polynuclear neutrophils(g/l) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Polynuclear neutrophils(g/l) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Polynuclear neutrophils(g/l) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Polynuclear neutrophils(g/l) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Mean corpuscular volume (µ^3) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Mean corpuscular volume (µ^3) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Mean corpuscular volume (µ^3) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Mean corpuscular volume (µ^3) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Mean corpuscular volume (µ^3) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Mean corpuscular volume (µ^3) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only

  • Monocytes (g/l) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Monocytes (g/l) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Monocytes (g/l) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Monocytes (g/l) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Monocytes (g/l) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Monocytes (g/l) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Mean corpuscular hemoglobin (pg/GR) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Mean corpuscular hemoglobin (pg/GR) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Mean corpuscular hemoglobin (pg/GR) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Mean corpuscular hemoglobin (pg/GR) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Mean corpuscular hemoglobin (pg/GR) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Mean corpuscular hemoglobin (pg/GR) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Lymphocytes (g/l) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Lymphocytes (g/l) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Lymphocytes (g/l) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Lymphocytes (g/l) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Lymphocytes (g/l) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Lymphocytes (g/l) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear eosinophils (g/l) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear eosinophils (g/l) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear eosinophils (g/l) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear eosinophils (g/l) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear eosinophils (g/l) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear eosinophils (g/l) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear basophils (g/l) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear basophils (g/l) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear basophils (g/l) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear basophils (g/l) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear basophils (g/l) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Polynuclear basophils (g/l) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • D-dimers (ng/ml) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • D-dimers (ng/ml) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • D-dimers (ng/ml) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • D-dimers (ng/ml) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • D-dimers (ng/ml) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • D-dimers (ng/ml) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Fibrin monomers (ng/ml) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Fibrin monomers (ng/ml) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Fibrin monomers (ng/ml) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Fibrin monomers (ng/ml) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Fibrin monomers (ng/ml) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Fibrin monomers (ng/ml) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Trophoblast microparticles (%) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Trophoblast microparticles (%) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Trophoblast microparticles (%) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Trophoblast microparticles (%) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Trophoblast microparticles (%) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Trophoblast microparticles (%) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Angiogenic marker CD146 (ng/ml) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Angiogenic marker CD146 (ng/ml) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Angiogenic marker CD146 (ng/ml) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Angiogenic marker CD146 (ng/ml) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Angiogenic marker CD146 (ng/ml) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Angiogenic marker CD146 (ng/ml) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of nucleosomes (AU) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of nucleosomes (AU) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of nucleosomes (AU) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of nucleosomes (AU) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of nucleosomes (AU) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of nucleosomes (AU) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of free DNA (ng/ml) [ Time Frame: -1 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of free DNA (ng/ml) [ Time Frame: -2 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of free DNA (ng/ml) [ Time Frame: -3 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of free DNA (ng/ml) [ Time Frame: -4 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of free DNA (ng/ml) [ Time Frame: -5 months ] [ Designated as safety issue: No ]
    For group T2x only.

  • Total plasma concentration of free DNA (ng/ml) [ Time Frame: -6 months ] [ Designated as safety issue: No ]
    For group T2x only.


Biospecimen Retention:   Samples Without DNA

At each visit a total of 36 ml of blood will be drawn (5 x EDTA tube = 5 x 4.5ml; 2 x CTAD tube = 2 x 4.5 ml and 1 dry tube = 4.5 ml).

Tubes will be rapidly conditioned and samples stored at -80°C. After analysis, remaining samples will be stored in the Nîmes University Hospital Biological Collections.


Estimated Enrollment: 180
Study Start Date: July 2015
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Group P: pregnancy w/complications

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

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.
Group T1: Healthy volunteers

Healthy volunteers with no history of chronic or neoplastic disease.

30 healthy volunteers will be included.

Interventions to be administered: Bloodwork, baseline

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.
Group T2: Pregnancy, no complications

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

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.
Group T1x: 15 Healthy volunteers

15 Healthy volunteers randomly selected from group T1. These patients will have 2 additional months of follow up.

Interventions to be administered: Blood work, Months 1 & 2

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.
Biological: 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.
Group T2x: 15 Pregnancy, no complications

15 patients randomly selected from group T2; these patients will have 7 months of follow up during pregnancy.

Interventions to be administered: Bloodwork, Months -1 to -6

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.
Biological: 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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

The study population includes three groups:

Group P: 100 pregnant women with complications typical of placental vascular disease or venous thromboembolism.

Group T1: 30 non-pregnant, healthy volunteers

  • 15 patients will be randomly selected from group T1 to form group T1x. The latter group has two months of additional follow up.

Group T2: 50 pregnant, healthy volunteers

  • 15 patients will be randomly selected from group T2 to form group T2x. The latter group has 7 months of follow-up during pregnancy.
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
  • 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 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01736826

Contacts
Contact: Sylvie Bouvier, MD +33.(0)4.66.68.32.11 sylvie.bouvier@chu-nimes.fr
Contact: Carey M Suehs, PhD +33.(0)4.66.68.67.88 carey.suehs@chu-nimes.fr

Locations
France
CHU de Nîmes - Hôpital Universitaire Carémeau
Nîmes Cedex 9, France, 30029
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nīmes
Investigators
Study Director: Sylvie Bouvier, MD Centre Hospitalier Universitaire de Nîmes
Principal Investigator: Eve Mousty, MD Centre Hospitalier Universitaire de Nîmes
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier: NCT01736826     History of Changes
Other Study ID Numbers: LOCAL/2012/SB-01, 2014-A01120-47
Study First Received: November 27, 2012
Last Updated: November 18, 2014
Health Authority: France: Committee for the Protection of Personnes
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Centre Hospitalier Universitaire de Nīmes:
plasma nucleosome concentration
plasma free DNA concentration

Additional relevant MeSH terms:
Eclampsia
Fetal Death
HELLP Syndrome
Hypertension
Hypertension, Pregnancy-Induced
Placental Insufficiency
Pre-Eclampsia
Pulmonary Embolism
Thrombosis
Venous Thromboembolism
Venous Thrombosis
Cardiovascular Diseases
Death
Embolism
Embolism and Thrombosis
Lung Diseases
Pathologic Processes
Placenta Diseases
Pregnancy Complications
Respiratory Tract Diseases
Thromboembolism
Vascular Diseases

ClinicalTrials.gov processed this record on November 25, 2014