Multicentric Prospective Study of Genetic and Physiopathology Concerning Dysregulation of Complement During Repeated Fetal Abortions

The aim of the study is to assess the role of complement dysregulation and its impact on antiangiogenic factors (soluble Flt1 and endoglin) in patients with foetal losses.

Study Overview

• Status: Completed
• Conditions: Fetal Losses
• Intervention / Treatment: Other: blood sample

Detailed Description

Females with medical history of repeated foetal losses will have blood sampling to perform analyses. If pregnant, blood sampling will be performed at different times throughout the pregnancy.

Controls will be females without medical history of repeated foetal losses. They will also have blood sampling to perform analyses. If pregnant, blood sampling will be performed at different times throughout the pregnancy.

Blood analyses will focus on :

• mutations in genes coding for molecules that modulate complement activity
• serum levels of sFlt1 and endoglin and their link to complement activation

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• France
  • Clamart, France, 92141
    • Antoine Beclere Hospital (AP-HP)
  • Nantes, France, 44093
    • CHU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Females with medical history of repeated foetal losses and females without medical history of repeated foetal losses as controls.

Description

Inclusion Criteria:

• Inclusion criteria for females with repeated fetal losses:
• Age> 18
• Female affiliated to French health insurance (Social Security),
• Informed consent form signed
• Patient with history of at least three foetal losses without any cause found (chromosomal abnormalities, uterine malformations, endocrine disorders, etc.)

Exclusion criteria for females with repeated fetal losses :

• Patient not fulfilling inclusion criteria
• Age > 40
• Female unable to understand benefits and risks of protocol
• Female with history of repeated foetal losses of infectious or endocrine origin.

Inclusion criteria for females without repeated fetal losses:

• Age> 18
• Female affiliated to the French health insurance (Social Security)
• Informed consent form signed
• Female without history of repeated foetal losses

Exclusion criteria for females without repeated fetal losses:

• Patient not fulfilling inclusion criteria
• Female with age above 40
• Female unable to understand benefits and risks of protocol

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
females with medical history of repeated foetal losses; The females can be pregnant	Other: blood sample; blood sampling at inclusion and throughout pregnancy when pregnant
females without medical history of repeated foetal losses; The females can be pregnant	Other: blood sample; blood sampling at inclusion and throughout pregnancy when pregnant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mutations in genes coding for molecules that modulate complement activity	to determine frequency of mutations of genes (membrane-cofactor protein (MCP), decay accelerating factor (DAF), ....) involved in complement activation : Profiles of these genes will be analysed in blood sample of females with medical history of repeated foetal losses and compared to those analysed in blood sample of females without medical history of repeated foetal losses.	day1 (at inclusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum levels of sFlt1 and endoglin and their link to complement activation markers	To assess serum levels of sFlt1 and endoglin and their link to complement activation markers in blood samples removed throughout pregnancy of females with medical history of repeated foetal losses and throughout pregnancy of females without medical history of repeated foetal losses.	4 weeks post pregnancy start
serum levels of sFlt1 and endoglin and their link to complement activation	To assess serum levels of sFlt1 and endoglin and their link to complement activation markers in blood samples removed throughout pregnancy of females with medical history of repeated foetal losses and throughout pregnancy of females without medical history of repeated foetal losses.	8 weeks post pregnancy start
serum levels of sFlt1 and endoglin and their link to complement activation	To assess serum levels of sFlt1 and endoglin and their link to complement activation markers in blood samples removed throughout pregnancy of females with medical history of repeated foetal losses and throughout pregnancy of females without medical history of repeated foetal losses.	16 weeks post pregnancy start
serum levels of sFlt1 and endoglin and their link to complement activation	To assess serum levels of sFlt1 and endoglin and their link to complement activation markers in blood samples removed throughout pregnancy of females with medical history of repeated foetal losses and throughout pregnancy of females without medical history of repeated foetal losses.	24 weeks post pregnancy start

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: November 29, 2011
• First Submitted That Met QC Criteria: September 19, 2012
• First Posted (Estimate): September 24, 2012

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 14, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: complement; Foetal loss; antiangiogenic factors; Repeated fetal losses
• Other Study ID Numbers: 10/6-K