Monocyte Chemotactic Protein-1 (MCP-1) Expressing Monocytes to Predict Preterm Delivery: PhenoMAP Study (PHENOMAP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Centre Hospitalier Universitaire Dijon
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire Dijon
ClinicalTrials.gov Identifier:
NCT01340222
First received: April 19, 2011
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

The threat of preterm labour (PTL) is the first cause of hospitalization in the course of pregnancy. Its diagnostic is based on clinical examination with a positive predictive value of about 40 %. The role of the Monocyte chemotactic protein-1 (MCP-1) in delivery has been suggested by its secretion in the amniotic fluid during labour and by the increase in the expression of its RNA messengers in the peripheral maternal blood. We have also shown that the proportion of MCP-1-expressing monocytes is higher in women with vaginal delivery compared with those with caesarean delivery prior the onset of labour.

OBJECTIVES : Primary To seek link between the respective proportions of circulating maternal monocyte and lymphocyte subpopulations and the true onset of PTL characterised by delivery occurring within 7 days post admission. Secondary: to (1) compare the predictive values of these new markers with those currently used, e.g. quantification of fœtal fibronectin and assessment of cervical length and effacement, (2) Compare the respective proportions of monocytes and lymphocyte subpopulations in maternal blood and fœtal membranes, (3) determine if a correlation exists between the activation markers expressed by maternal monocyte and lymphocyte subpopulations and the neonatal outcomes of preterm infants.

MATERIAL AND METHODS: 200 patients with a singleton pregnancy between 24 and 34 weeks of amenorrhea and complicated PTL, will be prospectively included in the maternity wards of Galway (Ireland) and of Dijon with the support of the perinatal network of Burgundy. A 2X5ml blood sample will be collected upon admission, at D1, D2, D4 and D6 for women who did not deliver within the first 7 days; finally, another blood sample will be drawn upon discharge. After delivery, foetal membranes will be collected to characterize and compare the various monocyte and lymphocyte subpopulations in the maternal blood. The characterization and the study of the level of activation of blood and foetal membrane cells will be performed using flow cytometry technique with suitable markers. The main judgment criteria will be the percentage of monocytes positively expressing MCP-1 for all three monocyte subpopulations ("inflammatory", "residents or patrollers" and "intermediates", according to CD14, CD16, CCR2 and MCP-1 markers. Lymphocyte subpopulations will be assessed using the following markers: CD45, CD3, CD4, CD8 (T lymphocytes), HLA-DR (activated T lymphocytes), CD19 (B lymphocytes), CD16/CD56 (NK Cells), intracellular IFN-gamma (Th1 lymphocytes), intracellular IL-4 (Th-2 lymphocytes), intracellular IL-17 and CCR6 (Th17 lymphocytes), CD4, CD25, Foxp3 and CD127 (Tregs). Univariate statistical analysis of quantitative data will be performed using the Mann and Witney test or ANOVA, after verification of the conditions of application. The comparisons of percentages will be done using Chi-square Pearson tests and the Fisher's exact test, as appropriate. The multivariate analysis will be performed using a stepwise descending analysis.

TRANSLATIONAL DIMENSION: The characterization of the various monocyte and lymphocyte subpopulations in the maternal blood and in the foetal membranes might constitute an " immunological signature " of the labour and therefore validate the relevance of a predictive marker for clinicians.

EXPECTED RESULTS AND PERSPECTIVES: The study of the various monocyte and lymphocyte subpopulations in the maternal blood will allow to better characterise the immunological mechanisms occurring at the start of premature labour and to identity predictive markers of the preterm delivery, to validate prospectively in order to optimize the management of PTL


Condition Intervention
Preterm Labour
Biological: biological samples

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Evaluation of the Prognostic Value of Monocytes and Lymphocyte Phenotyping, Along With Intracellular MCP-1 Expression, to Predict Preterm Delivery for Women Hospitalized for Threat of Preterm Labor Between 24 and 34 Weeks of Amenorrhea: PhenoMAP Study

Further study details as provided by Centre Hospitalier Universitaire Dijon:

Primary Outcome Measures:
  • Number of women with delivering before 7 days [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Main outcome will be a delivery occurring within 7 days post admission for PTL. Women discharged from hospital before day 7 and not having delivered will not be censored; they will be classified as non-delivering before D7.


Estimated Enrollment: 200
Study Start Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: biological samples
    4 blood sampling will be made at J0, J2, J4, J6 befor delivery and 1 blood sampling 3 days after delivery
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Threat of preterm labour (PTL) occurring between 24 and 34 WOA, defined according to validated criteria i.e. by (1) the presence of regular uterine contractions, lasting at least 30 seconds at a frequency ≥ 4 contractions every 30 minutes and confirmed by an external tocogram, (2) a cervical dilation of 3 cm or greater, to focus on true preterm labour, for the nulliparous women and 1-3 cm among primiparous women or multiparous and (3) a cervical obliteration >50%, or a cervix less than 25mm according to the echography, when this information is available. The first two criteria being mandatory, the third one optional as it is more subjective, or less likely to be available for every patient.

    • Singleton pregnancy

Exclusion Criteria:

  • Pre-existing diabetes or gestational diabetes, morbid obesity (BMI > 35 kg/m2) as these situations modify the expression of MCP-1.

    • Woman presenting a spontaneous rupture of membranes (SRM) with confirmed or probable chorioamniotitis
    • Inflammatory or auto-immune disease
    • Suspected or confirmed infectious disease, including HIV, HCV, HBV
    • Anti-inflammatory drug treatment or immuno-modulator.
    • Multiple pregnancies
    • PTL <24 WOA or >34 WOA
    • Patient less than 18 years of age.
    • Patient not affiliated to social security insurance
  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: NCT01340222

Contacts
Contact: Marc BARDOU, MD 3.80.39.34.33 ext 33 marc.bardou@u-bourgogne.fr

Locations
France
Centre d'investigation clinique plurithématique Recruiting
Dijon, France, 21079
Contact: Marc BARDOU, MD    644 16 02 18 ext 33    marc.bardou@u-bourgogne.fr   
Principal Investigator: Paul SAGOT, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire Dijon
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire Dijon
ClinicalTrials.gov Identifier: NCT01340222     History of Changes
Other Study ID Numbers: SAGOT PHRC IR 2010
Study First Received: April 19, 2011
Last Updated: January 4, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Hospitalier Universitaire Dijon:
Preterm labour
monocyte
lymphocyte
MCP-1
Treg Lymphocytes
biologic markers
immunology
HLA-DR
Th17

Additional relevant MeSH terms:
Obstetric Labor, Premature
Premature Birth
Obstetric Labor Complications
Pregnancy Complications

ClinicalTrials.gov processed this record on October 29, 2014