Free DNA and Nucleosome Concentrations in Pathological Pregnancies

NCT01736826 | Completed

• 2 other identifiers: LOCAL/2012/SB-012014-A01120-47
• Study Type: observational
• Target: 137
• Locations: 1 country
• Sites: 1

Brief Summary

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

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

Conditions

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

Keywords

plasma nucleosome concentration; plasma free DNA concentration

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (149)

• Hemoglobin (g/l)

  baseline (day 0)

• Platelets (g/l)

  baseline (day 0)

• Leukocytes (g/l)

  baseline (day 0)

• Polynuclear neutrophils(g/l)

  baseline (day 0)

• Mean corpuscular volume (fL)

  baseline (day 0)

Study Arms (5)

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

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

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

Group T1x: 15 Healthy volunteers

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

Biological: Bloodwork, baseline; Biological: Blood work, Months 1 & 2

Group T2x: 15 Pregnancy, no complications

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

Biological: Bloodwork, baseline; Biological: Bloodwork, Months -1 to -6

Interventions

Bloodwork, baseline BIOLOGICAL

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 P: pregnancy w/complications; Group T1: Healthy volunteers; Group T1x: 15 Healthy volunteers; Group T2: Pregnancy, no complications; Group T2x: 15 Pregnancy, no complications

Blood work, Months 1 & 2 BIOLOGICAL

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 T1x: 15 Healthy volunteers

Bloodwork, Months -1 to -6 BIOLOGICAL

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.

Group T2x: 15 Pregnancy, no complications

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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 * The first 15 patients from group T1 will form group T1x. The latter group has two months of additional follow up. Group T2: 50 pregnant, healthy volunteers * The first 15 patients from group T2 will form group T2x. The latter group has 7 months of follow-up during pregnancy.

You may qualify if:

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

You may not qualify if:

• 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 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)
• Twin or multiple pregnancy
• 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)

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (1)

CHU de Nîmes - Hôpital Universitaire Carémeau

Nîmes, 30029, France

Location

Related Publications (2)

• Bouvier S, Mousty E, Fortier M, Demattei C, Mercier E, Nouvellon E, Chea M, Grosjean F, Letouzey V, Gris JC. Placenta-mediated complications: Nucleosomes and free DNA concentrations differ depending on subtypes. J Thromb Haemost. 2020 Dec;18(12):3371-3380. doi: 10.1111/jth.15105. Epub 2020 Oct 18.

  PMID: 32979032 RESULT

• Bouvier S, Traboulsi W, Blois SM, Demattei C, Joshkon A, Mousty E, Nollet M, Paulmyer-Lacroix O, Foucault-Bertaud A, Fortier M, Leroyer AS, Bachelier R, Letouzey V, Alfaidy N, Dignat-George F, Blot-Chabaud M, Gris JC, Bardin N. Soluble CD146 is increased in preeclampsia and interacts with galectin-1 to regulate trophoblast migration through VEGFR2 receptor. F S Sci. 2022 Feb;3(1):84-94. doi: 10.1016/j.xfss.2021.11.002. Epub 2021 Nov 19.

  PMID: 35559998 DERIVED

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.

MeSH Terms

Conditions

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

Interventions

BaseLine dental cement

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Placenta Diseases

Study Officials

• Sylvie Bouvier, MD

  Centre Hospitalier Universitaire de Nîmes

  STUDY DIRECTOR

• Eve Mousty, MD

  Centre Hospitalier Universitaire de Nîmes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2012
• First Posted: November 29, 2012
• Study Start: June 1, 2015
• Primary Completion: December 11, 2017
• Study Completion: December 11, 2017
• Last Updated: November 21, 2025

Record last verified: 2019-01

Locations

FR (1)