PAR Family Polymorphisms and Placental Invasion Disorders
Recruitment status was: Not yet recruiting
|First Received Date ICMJE||January 22, 2007|
|Last Updated Date||January 25, 2007|
|Start Date ICMJE||March 2007|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00425867 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||PAR Family Polymorphisms and Placental Invasion Disorders|
|Official Title ICMJE||Not Provided|
|Brief Summary||The present study will be undertaken to establish whether genetic variations of PAR1 could be involved in the occurrence of any of the "placental syndromes" of preterm delivery, preeclampsia, and/or small for gestational age babies and recurrent pregnancy loss.|
Polymorphisms of Protease Activated Receptor 1 and adverse pregnancy outcomes Protease Activated Receptor 1 (PAR1), the main thrombin receptor on vascular cells (Coughlin,1999), plays a critical role in orchestrating human placentation based on temporally and spatially constrained PAR1 expression in the normal invasive trophoblasts (O’Brien et al, 2003) and its overexpression in pathological invasive trophoblast (Even-Ram et al, 2003).
Various proteases of the PAR family as well as matrix metalloproteinases have been implicated in ancillary regulation of cancer metastases and tumor-related angiogenesis. PAR1 in particular has been proposed to be involved in invasive processes of various cancers (Ruf & Mueller, 2006; Boire et al, 2005). Similarly, it might be surmised that remodeling of the placenta microenvironment as well as the requisites of trophoblast invasiveness may be PAR1 sensitive (Grisaru-Granovsky et al, 2005). Therefore, one might hypothesize that PAR1 gene variability may be involved in early placentation and that adverse pregnancy outcomes of the "placental syndromes" may have their origin in PAR1 dysregulation.
Study Design: This is a prospective case-control pilot study. Subject enrolment and data collection will be performed via the Admission Service of the Division for Maternal & Fetal Medicine in a large tertiary obstetrics department in Jerusalem, Israel. Demographic data including maternal characteristics, past reproductive history, and information about previous complications during pregnancy, delivery and the neonatal period will be culled. The blood samples will be collected at routine admission after obtaining informed consent by the physician on the floor.
Four groups are described: patients with spontaneous preterm delivery of a singleton before 35 weeks of gestation; patients with a singleton pregnancy complicated by preeclampsia diagnosed according the Working Group Criteria (2000); patients who deliver a small for gestational age (SGA) singleton defined as a birth weight below the 10th percentile for the gestational age according to the Israeli growth curves (Dollberg et al, 2005); and for comparison, patients who deliver a singleton at term with appropriate size for gestational age. Patients who suffer delivery with intrauterine fetal demise and/or neonates with malformations will be excluded.
Maternal and umbilical cord blood samples (in 0.11mol/l sodium tri citrate) will be paired. DNA will be prepared from white blood cells by standard techniques and subsequently stored at -4°C for batched analysis. The laboratory staff will be blinded as to the clinical status of the samples.
Polymorphism analysis will be performed for the following polymorphisms of the PAR1 gene: [-1426CT], [506 insertion of 13 bp],[IVS-14A/T]: as per standard PCR techniques using appropriate restriction endonucleases (Arnaud et l, 2000).
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case Control
Primary Purpose: Screening
Time Perspective: Cross-Sectional
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Behavioral: PAR1 polymoprhisms and placental invasion|
|Study Groups/Cohorts||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Completion Date||November 2007|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||20 Years to 40 Years (Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Not Provided|
|Removed Location Countries|
|NCT Number ICMJE||NCT00425867|
|Other Study ID Numbers ICMJE||PAR1 polymorphisms|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Shaare Zedek Medical Center|
|Collaborators ICMJE||Not Provided|
|PRS Account||Shaare Zedek Medical Center|
|Verification Date||January 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP