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Completed

NCT Number: NCT01736826

Free DNA and Nucleosome Concentrations in Pathological Pregnancies

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).

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Key information

About this study

Our secondary objectives include the following:

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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.

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.

Primary outcomes

  1. Total plasma concentration of free DNA (ng/ml)

    Time frame: 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.

  2. Total plasma concentration of nucleosomes (AU)

    Time frame: 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 outcomes

  1. Hemoglobin (g/l)

    Time frame: baseline (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.

  2. Platelets (g/l)

    Time frame: baseline (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.

  3. Leukocytes (g/l)

    Time frame: baseline (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.

  4. Polynuclear neutrophils(g/l)

    Time frame: baseline (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.

  5. Mean corpuscular volume (fL)

    Time frame: baseline (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.

  6. Monocytes (g/l)

    Time frame: baseline (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.

  7. Mean corpuscular hemoglobin (pg/GR)

    Time frame: baseline (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.

  8. Lymphocytes (g/l)

    Time frame: baseline (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.

  9. Polynuclear eosinophils (g/l)

    Time frame: baseline (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.

  10. Polynuclear basophils (g/l)

    Time frame: baseline (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.

  11. D-dimers (ng/ml)

    Time frame: baseline (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.

  12. Fibrin monomers (ng/ml)

    Time frame: baseline (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.

  13. Trophoblast microparticles (%)

    Time frame: baseline (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.

  14. Angiogenic marker CD146 (ng/ml)

    Time frame: baseline (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.

  15. Hemoglobin (g/l)

    Time frame: 1 month

    For group T1x only

  16. Platelets (g/l)

    Time frame: 1 month

    For group T1x only

  17. Leukocytes (g/l)

    Time frame: 1 month

    For group T1x only

  18. Polynuclear neutrophils(g/l)

    Time frame: 1 month

    For group T1x only

  19. Mean corpuscular volume (fL)

    Time frame: 1 month

    For group T1x only

  20. Monocytes (g/l)

    Time frame: 1 month

    For group T1x only

  21. Mean corpuscular hemoglobin (pg/GR)

    Time frame: 1 month

    For group T1x only

  22. Lymphocytes (g/l)

    Time frame: 1 month

    For group T1x only

  23. Polynuclear eosinophils (g/l)

    Time frame: 1 month

    For group T1x only

  24. Polynuclear basophils (g/l)

    Time frame: 1 month

    For group T1x only

  25. D-dimers (ng/ml)

    Time frame: 1 month

    For group T1x only

  26. Fibrin monomers (ng/ml)

    Time frame: 1 month

    For group T1x only

  27. Trophoblast microparticles (%)

    Time frame: 1 month

    For group T1x only

  28. Angiogenic marker CD146 (ng/ml)

    Time frame: 1 month

    For group T1x only

  29. Total plasma concentration of free DNA (ng/ml)

    Time frame: 1 month

    For group T1x only

  30. Total plasma concentration of nucleosomes (AU)

    Time frame: 1 month

    For group T1x only

  31. Hemoglobin (g/l)

    Time frame: 2 months

    For group T1x only

  32. Platelets (g/l)

    Time frame: 2 months

    For group T1x only

  33. Leukocytes (g/l)

    Time frame: 2 months

    For group T1x only

  34. Polynuclear neutrophils(g/l)

    Time frame: 2 months

    For group T1x only

  35. Mean corpuscular volume (fL)

    Time frame: 2 months

    For group T1x only

  36. Monocytes (g/l)

    Time frame: 2 months

    For group T1x only

  37. Mean corpuscular hemoglobin (pg/GR)

    Time frame: 2 months

    For group T1x only

  38. Lymphocytes (g/l)

    Time frame: 2 months

    For group T1x only

  39. Polynuclear eosinophils (g/l)

    Time frame: 2 months

    For group T1x only

  40. Polynuclear basophils (g/l)

    Time frame: 2 months

    For group T1x only

  41. D-dimers (ng/ml)

    Time frame: 2 months

    For group T1x only

  42. Fibrin monomers (ng/ml)

    Time frame: 2 months

    For group T1x only

  43. Trophoblast microparticles (%)

    Time frame: 2 months

    For group T1x only

  44. Angiogenic marker CD146 (ng/ml)

    Time frame: 2 months

    For group T1x only

  45. Total plasma concentration of free DNA (ng/ml)

    Time frame: 2 months

    For group T1x only

  46. Total plasma concentration of nucleosomes (AU)

    Time frame: 2 months

    For group T1x only

  47. Hemoglobin (g/l)

    Time frame: -1 months

    For group T2x only

  48. Hemoglobin (g/l)

    Time frame: -2 months

    For group T2x only

  49. Hemoglobin (g/l)

    Time frame: -3 months

    For group T2x only

  50. Hemoglobin (g/l)

    Time frame: -4 months

    For group T2x only

  51. Hemoglobin (g/l)

    Time frame: -5 months

    For group T2x only

  52. Hemoglobin (g/l)

    Time frame: -6 months

    For group T2x only

  53. Platelets (g/l)

    Time frame: -1 months

    For group T2x only

  54. Platelets (g/l)

    Time frame: -2 months

    For group T2x only

  55. Platelets (g/l)

    Time frame: -3 months

    For group T2x only

  56. Platelets (g/l)

    Time frame: -4 months

    For group T2x only

  57. Platelets (g/l)

    Time frame: -5 months

    For group T2x only

  58. Platelets (g/l)

    Time frame: -6 months

    For group T2x only

  59. Leukocytes (g/l)

    Time frame: -1 months

    For group T2x only

  60. Leukocytes (g/l)

    Time frame: -2 months

    For group T2x only

  61. Leukocytes (g/l)

    Time frame: -3 months

    For group T2x only

  62. Leukocytes (g/l)

    Time frame: -4 months

    For group T2x only

  63. Leukocytes (g/l)

    Time frame: -5 months

    For group T2x only

  64. Leukocytes (g/l)

    Time frame: -6 months

    For group T2x only

  65. Polynuclear neutrophils(g/l)

    Time frame: -1 months

    For group T2x only

  66. Polynuclear neutrophils(g/l)

    Time frame: -2 months

    For group T2x only

  67. Polynuclear neutrophils(g/l)

    Time frame: -3 months

    For group T2x only

  68. Polynuclear neutrophils(g/l)

    Time frame: -4 months

    For group T2x only

  69. Polynuclear neutrophils(g/l)

    Time frame: -5 months

    For group T2x only

  70. Polynuclear neutrophils(g/l)

    Time frame: -6 months

    For group T2x only

  71. Mean corpuscular volume (fL)

    Time frame: -1 months

    For group T2x only

  72. Mean corpuscular volume (fL)

    Time frame: -2 months

    For group T2x only

  73. Mean corpuscular volume (fL)

    Time frame: -3 months

    For group T2x only

  74. Mean corpuscular volume (fL)

    Time frame: -4 months

    For group T2x only

  75. Mean corpuscular volume (fL)

    Time frame: -5 months

    For group T2x only

  76. Mean corpuscular volume (fL)

    Time frame: -6 months

    For group T2x only

  77. Monocytes (g/l)

    Time frame: -1 months

    For group T2x only.

  78. Monocytes (g/l)

    Time frame: -2 months

    For group T2x only.

  79. Monocytes (g/l)

    Time frame: -3 months

    For group T2x only.

  80. Monocytes (g/l)

    Time frame: -4 months

    For group T2x only.

  81. Monocytes (g/l)

    Time frame: -5 months

    For group T2x only.

  82. Monocytes (g/l)

    Time frame: -6 months

    For group T2x only.

  83. Mean corpuscular hemoglobin (pg/GR)

    Time frame: -1 months

    For group T2x only.

  84. Mean corpuscular hemoglobin (pg/GR)

    Time frame: -2 months

    For group T2x only.

  85. Mean corpuscular hemoglobin (pg/GR)

    Time frame: -3 months

    For group T2x only.

  86. Mean corpuscular hemoglobin (pg/GR)

    Time frame: -4 months

    For group T2x only.

  87. Mean corpuscular hemoglobin (pg/GR)

    Time frame: -5 months

    For group T2x only.

  88. Mean corpuscular hemoglobin (pg/GR)

    Time frame: -6 months

    For group T2x only.

  89. Lymphocytes (g/l)

    Time frame: -1 months

    For group T2x only.

  90. Lymphocytes (g/l)

    Time frame: -2 months

    For group T2x only.

  91. Lymphocytes (g/l)

    Time frame: -3 months

    For group T2x only.

  92. Lymphocytes (g/l)

    Time frame: -4 months

    For group T2x only.

  93. Lymphocytes (g/l)

    Time frame: -5 months

    For group T2x only.

  94. Lymphocytes (g/l)

    Time frame: -6 months

    For group T2x only.

  95. Polynuclear eosinophils (g/l)

    Time frame: -1 months

    For group T2x only.

  96. Polynuclear eosinophils (g/l)

    Time frame: -2 months

    For group T2x only.

  97. Polynuclear eosinophils (g/l)

    Time frame: -3 months

    For group T2x only.

  98. Polynuclear eosinophils (g/l)

    Time frame: -4 months

    For group T2x only.

  99. Polynuclear eosinophils (g/l)

    Time frame: -5 months

    For group T2x only.

  100. Polynuclear eosinophils (g/l)

    Time frame: -6 months

    For group T2x only.

  101. Polynuclear basophils (g/l)

    Time frame: -1 months

    For group T2x only.

  102. Polynuclear basophils (g/l)

    Time frame: -2 months

    For group T2x only.

  103. Polynuclear basophils (g/l)

    Time frame: -3 months

    For group T2x only.

  104. Polynuclear basophils (g/l)

    Time frame: -4 months

    For group T2x only.

  105. Polynuclear basophils (g/l)

    Time frame: -5 months

    For group T2x only.

  106. Polynuclear basophils (g/l)

    Time frame: -6 months

    For group T2x only.

  107. D-dimers (ng/ml)

    Time frame: -1 months

    For group T2x only.

  108. D-dimers (ng/ml)

    Time frame: -2 months

    For group T2x only.

  109. D-dimers (ng/ml)

    Time frame: -3 months

    For group T2x only.

  110. D-dimers (ng/ml)

    Time frame: -4 months

    For group T2x only.

  111. D-dimers (ng/ml)

    Time frame: -5 months

    For group T2x only.

  112. D-dimers (ng/ml)

    Time frame: -6 months

    For group T2x only.

  113. Fibrin monomers (ng/ml)

    Time frame: -1 months

    For group T2x only.

  114. Fibrin monomers (ng/ml)

    Time frame: -2 months

    For group T2x only.

  115. Fibrin monomers (ng/ml)

    Time frame: -3 months

    For group T2x only.

  116. Fibrin monomers (ng/ml)

    Time frame: -4 months

    For group T2x only.

  117. Fibrin monomers (ng/ml)

    Time frame: -5 months

    For group T2x only.

  118. Fibrin monomers (ng/ml)

    Time frame: -6 months

    For group T2x only.

  119. Trophoblast microparticles (%)

    Time frame: -1 months

    For group T2x only.

  120. Trophoblast microparticles (%)

    Time frame: -2 months

    For group T2x only.

  121. Trophoblast microparticles (%)

    Time frame: -3 months

    For group T2x only.

  122. Trophoblast microparticles (%)

    Time frame: -4 months

    For group T2x only.

  123. Trophoblast microparticles (%)

    Time frame: -5 months

    For group T2x only.

  124. Trophoblast microparticles (%)

    Time frame: -6 months

    For group T2x only.

  125. Angiogenic marker CD146 (ng/ml)

    Time frame: -1 months

    For group T2x only.

  126. Angiogenic marker CD146 (ng/ml)

    Time frame: -2 months

    For group T2x only.

  127. Angiogenic marker CD146 (ng/ml)

    Time frame: -3 months

    For group T2x only.

  128. Angiogenic marker CD146 (ng/ml)

    Time frame: -4 months

    For group T2x only.

  129. Angiogenic marker CD146 (ng/ml)

    Time frame: -5 months

    For group T2x only.

  130. Angiogenic marker CD146 (ng/ml)

    Time frame: -6 months

    For group T2x only.

  131. Total plasma concentration of nucleosomes (AU)

    Time frame: -1 months

    For group T2x only.

  132. Total plasma concentration of nucleosomes (AU)

    Time frame: -2 months

    For group T2x only.

  133. Total plasma concentration of nucleosomes (AU)

    Time frame: -3 months

    For group T2x only.

  134. Total plasma concentration of nucleosomes (AU)

    Time frame: -4 months

    For group T2x only.

  135. Total plasma concentration of nucleosomes (AU)

    Time frame: -5 months

    For group T2x only.

  136. Total plasma concentration of nucleosomes (AU)

    Time frame: -6 months

    For group T2x only.

  137. Total plasma concentration of free DNA (ng/ml)

    Time frame: -1 months

    For group T2x only.

  138. Total plasma concentration of free DNA (ng/ml)

    Time frame: -2 months

    For group T2x only.

  139. Total plasma concentration of free DNA (ng/ml)

    Time frame: -3 months

    For group T2x only.

  140. Total plasma concentration of free DNA (ng/ml)

    Time frame: -4 months

    For group T2x only.

  141. Total plasma concentration of free DNA (ng/ml)

    Time frame: -5 months

    For group T2x only.

  142. Total plasma concentration of free DNA (ng/ml)

    Time frame: -6 months

    For group T2x only.

  143. Fibrinogen (g/l)

    Time frame: 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.

  144. Fibrinogen (g/l)

    Time frame: -1 months

    For group T2x only.

  145. Fibrinogen (g/l)

    Time frame: -2 months

    For group T2x only.

  146. Fibrinogen (g/l)

    Time frame: -3 months

    For group T2x only.

  147. Fibrinogen (g/l)

    Time frame: -4 months

    For group T2x only.

  148. Fibrinogen (g/l)

    Time frame: -5 months

    For group T2x only.

  149. Fibrinogen (g/l)

    Time frame: -6 months

    For group T2x only.

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Nīmes

Other

Registry information

Official study title

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

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Nov 29, 2012
Registry last updated
Nov 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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