Clinical Trial: EVERREST Developing a Therapy for Fetal Growth Restriction

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: EVERREST - Developing a Therapy for Fetal Growth Restriction. A 6 Year Prospective Study to Define the Clinical and Biological Characteristic of Pregnancies Affected by Se

Brief Summary:

Fetal Growth Restriction (FGR) is a major obstetric problem, affecting 1.46 million fetuses worldwide each year and contributing to 50% of stillbirths. Severe early onset FGR affects 1 in 500 pregnancies, leading to stillbirth or the need for delivery before 28 weeks gestation. The combination of FGR and prematurity is associated with a significant risk of neonatal mortality and short and long-term complications. Even modest increases in birthweight (e.g from 500 to 600g) and gestation at delivery (e.g from 26 to 27 weeks) are associated with significantly better outcomes but there are currently no treatments.

The EVERREST Clinical Trial, funded by the European Commission, aims to develop a treatment which will increase fetal growth in severe early onset FGR. It will use gene therapy injected into the uterine arteries of the mother to increase the levels of vascular endothelial growth factor (VEGF) and so increase uterine artery blood flow and fetal growth.

The EVERREST prospective study aims to form a clinical database and biobank of pregnancies affected by severe early onset FGR to improve understanding of the condition and serve as a comparison to assess the safety and efficacy of this intervention.

The prospective study will take place across four European centers who will later take part in the EVERREST Clinical Trial. Women with singleton fetuses with early onset FGR will be approached to take part in the study. Participating women will provide blood samples, details of their clinical condition, samples of umbilical cord blood, placenta and myometrial and placental bed biopsies at the time of Caesarean section (if needed). Data on short and long-term outcomes of the babies will be collected. All data will be entered onto a central database for eventual use as a compar

Detailed Summary:

Purpose and design Fetal growth restriction (FGR) is a serious condition affecting 8% of all pregnancies and contributing to 50% of stillbirths. Severe early onset FGR affects 1 in 500 pregnancies and occurs before 28 weeks gestation. As yet there are no therapies that improve fetal growth in utero.

The EVERREST Consortium are currently developing a treatment for FGR using gene therapy to increase levels of vascular endothelial growth factor (VEGF) in the mother's uterine arteries. Although in some cases severe early onset FGR is caused by chromosomal abnormalities or maternal infections, it is most commonly due to inadequate uteroplacental blood flow. VEGF, which is secreted by the placenta, is a vasodilator and mediates vasculogenesis and angiogenesis. In FGR, however, maternal serum levels of VEGF are significantly lower than in normal pregnancy. Previous studies in sheep and guinea pig models of FGR have shown that administering adenovirus VEGF gene therapy (Ad.VEGF) into the maternal uterine arteries safely increases fetal growth.

The EVERREST Consortium plans to carry out a phase I/II trial to assess the safety and efficacy of intra-uterine artery Ad.VEGF in women with pregnancies affected by severe early onset FGR. This will be called the EVERREST Clinical Trial. As these pregnancies have high rates of fetal mortality and morbidity it is vital to have up-to-date, reliable outcome data on untreated pregnancies with which to compare outcomes in the clinical trial.

The prospective study which this application is for will clinically and biochemically characterise a cohort of pregnancies affected by severe early onset FGR across the four European centres which will later be taking part in the clinical trial. A database will be created containing information about antenata
Sponsor: University College, London

Current Primary Outcome: data collection from pregnancies affected by severe early onset FGR. [ Time Frame: each hospital visit and up to 2 years follow up for babies ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University College, London

Dates:
Date Received: October 31, 2013
Date Started: March 2014
Date Completion: March 2021
Last Updated: October 26, 2016
Last Verified: May 2015