Ignite Creation Date:
2024-07-17 @ 11:39 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06464159
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-18
First Post:
2024-06-03
Brief Title:
New Therapeutic Strategy Against Preeclampsia
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
New Therapeutic Strategy Against Preeclampsia Angiogenic Switch to Physiological State by Extracorporeal Removal of sFlt-1 and Release of PlGF
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
APHERESE2
Brief 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 mothers 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
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
Detailed Description:
The aim of this biobank is to setup a collection of maternal plasma and serum from patients with preeclampsia and patients with normal pregnancy Assays of circulating angiogenic and anti-angiogenic factors free and total forms will be carried out on these serum and plasma at the hormonology laboratory in Cochin hospital Paris France These results will make it possible to optimize and validate the development of extracorporeal sFlt-1 purification techniques
Preeclampsia is a very heterogeneous disease in its clinical presentation our hypothesis is that this heterogeneity corresponds to different profiles of angiogenic balance disturbance Not all patients are likely to have the same expected benefit from extracorporeal clearance of sFlt-1 The objective is to assess the overall angiogenic balance on a large number of patients in order to determine which profile best corresponds to the indication for apheresis
A prospective non-interventional study will be initiated to collect maternal blood samples during normal pregnancies and during pregnancies complicated by preeclampsia Port-Royal Maternity Cochin APHP Blood samples will be collected after collection of written informed consent from 50 patients with preeclampsia and 50 patients without hypertensive disease
Between 20WG and 23WG6D 10 patients with PE and 10 patients with NP
Between 24WG and 27WG6D 10 patients with PE and 10 patients with NP
Between 28WG and 31WG6D 10 patients with PE and 10 patients with NP
Between 32WG and 35WG6D 10 patients with PE and 10 patients with NP
Between 36WG and 40WG6D 10 patients with PE and 10 patients with NP Inclusion of the patients will be performed through the Cochin maternalneonatal investigation center
Preeclampsia is a very heterogeneous disease in its clinical presentation our hypothesis is that this heterogeneity corresponds to different profiles of angiogenic balance disturbance Not all patients are likely to have the same expected benefit from extracorporeal clearance of sFlt-1 The objective is to assess the overall angiogenic balance on a large number of patients in order to determine which profile best corresponds to the indication for apheresis
A prospective non-interventional study will be initiated to collect maternal blood samples during normal pregnancies and during pregnancies complicated by preeclampsia Port-Royal Maternity Cochin APHP Blood samples will be collected after collection of written informed consent from 50 patients with preeclampsia and 50 patients without hypertensive disease
Between 20WG and 23WG6D 10 patients with PE and 10 patients with NP
Between 24WG and 27WG6D 10 patients with PE and 10 patients with NP
Between 28WG and 31WG6D 10 patients with PE and 10 patients with NP
Between 32WG and 35WG6D 10 patients with PE and 10 patients with NP
Between 36WG and 40WG6D 10 patients with PE and 10 patients with NP Inclusion of the patients will be performed through the Cochin maternalneonatal investigation center
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2023-A01545-40 | OTHER | None | None |