New Therapeutic Strategy Against Preeclampsia
NCT Number: NCT06464159
Acronym: APHERESE2
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Preeclampsia
Interventions: BIOLOGICAL: Biological collection
Sponsor: Assistance Publique - Hôpitaux de Paris
Sex: FEMALE
Age: ADULT
Enrollment: 100
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-06
Completion Date: 2026-11
Locations: Maternité Port-Royal, Paris, 75014, France

Summary:
Preeclampsia is a hypertensive disorder of pregnancy associated with important maternal and perinatal mortality. It complicates 2 to 5% of pregnancies and causes more than 70 000 maternal deaths each year worldwide. Although symptomatic management has improved there is currently no curative treatment, and only childbirth and delivery of the placenta, usually prematurely, alleviate the mother's symptoms. The management of extremely preterm infants is a major societal challenge in medical, ethical and economic terms.

Placental insufficiency plays a central role in the pathophysiology of preeclampsia. Abnormal placentation during the first trimester leads to placental hypoperfusion, which induces trophoblast dysfunction and the release in maternal circulation of trophoblastic factors leading to the maternal symptoms. Among molecules that participate to the pathophysiology of preeclampsia, one of the most important players is soluble fms-like tyrosine kinase 1 (sFlt-1), which is a soluble form of the vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) receptor. sFlt-1 binds to free VEGF and PlGF in the maternal circulation, thus reducing their bioavailability for their membrane receptors. Targeting the sFlt-1 pathway is one of the most promising strategies for the development of new treatments for preeclampsia. As sFlt-1 results from alternative splicing, its peptide sequence is identical to that of the extracellular part of the membrane receptor. The development of drugs that act specifically on the soluble form and not on the membrane form is therefore particularly complex.

The general objective of this research is to restore the angiogenic balance that maintains the physiological concentrations of free angiogenic factors in order to significantly prolong the pregnancy and diminish the consequences of the great prematurity. The precise objectives of the APHERESE 2 project are:

1. To transpose the proof of concept of the APHERESE1 project to the scale of a real apheresis column
2. To develop an innovative assay technology to determine the global circulating angiogenic balance for each patient

Primary Outcome Measures: Concentration of total sFlt-1, in pg/mL - to assess main angiogenic factors during PE, intra uterine growth restriction (IUGR) and normal pregnancy, 6 months|Concentration of free PlGF, in pg/mL - to assess main angiogenic factors during PE, intra uterine growth restriction (IUGR) and normal pregnancy, 6 months
Secondary Outcome Measures: Concentration of total PIGF, in pg/mL - to assess global circulating angiogenic balance during PE, intra uterine growth restriction (IUGR) and normal pregnancy, 6 months|Concentration of total VEGFA, in pg/mL - to assess global circulating angiogenic balance during PE, intra uterine growth restriction (IUGR) and normal pregnancy, 6 months|Concentration of total sVEGFR2, in pg/mL - to assess global circulating angiogenic balance, total VEGFA and total sVEGFR2 during PE, intra uterine growth restriction (IUGR) and normal pregnancy, 6 months