NCT06249178

EV Based Platform for Monitoring Therapeutics Response During Pregnancy (ARISE)

Developing Extracellular Vesicle Based MPRINT Translational Resource Platform for Monitoring Therapeutics Response During Pregnancy

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 1,000 (estimated)
• Sponsor: Ohio State University · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this prospective observational cohort study of pregnant people at-risk of preeclampsia receiving aspirin as part of clinical care or a planned randomized controlled trial of 81mg vs. 162mg of aspirin is to generate proteomic data to show a distinct maternal and fetal Extracellular Vesicle (EV) proteome profile with aspirin treatment, and develop and validate a multi-marker panel for the monitoring of placental function in people at-risk of Preeclampsia and in response to aspirin treatment. The primary research question is: 1\. Does the maternal and fetal Positive for Placental Alkaline Phosphatase (PLAP+) Extracellular Vesicle (EV) proteome profile in the 2nd and 3rd trimester of pregnancy differ between people who receive aspirin and develop (or not) preeclampsia? Participants will be asked to give blood samples up to four times during and at the end of their pregnancy.

Detailed description

Pregnant and lactating people remain therapeutic orphans as they are excluded from the vast majority of clinical drug development and therapeutic trials. Moreover, current practices in drug evaluation in pregnancy have been hindered by the lack of effective biomarkers and innovative study designs. There is a need to develop novel placental-specific biomarkers in order to assess placental function and response to therapeutics, as a way to inform on their safety and efficacy. An example of these novel biomarkers is placental (fetal) specific extracellular vesicles (EVs). Recent advances in characterizing the cargo content of these EVs demonstrated their potential to be used as placental biomarkers. Fourteen proteins found in EVs significantly correlated with aspirin use (FDR\<0.1) in at-risk people, but that more power is needed to confidently assess the relationship with aspirin dosage and pregnancy outcomes. In addition, prior studies showed that aspirin affects endothelial and trophoblast cells, thus potentially modulating exosome derived from these cells and their cargo contents. The main goal is to develop a novel platform using exosome profiling, as novel biomarkers, to monitor placental mediated adverse pregnancy outcomes and response to therapeutics. Specific Aim 1: Develop and validate a multi-marker panel/Extracellular Vesicle (EV) proteome profile (maternal and fetal) for monitoring of placental/fetal membrane function in people at-risk of Preeclampsia (PE) and in response to aspirin treatment. Specific Aim 2: Demonstrate that maternal and fetal Positive for Placental Alkaline Phosphatase (PLAP+) EV proteome profile in the 2nd and 3rd trimester of pregnancy differ between people who develop (or not) preeclampsia and correlate with aspirin dose and salicylic acid concentrations. Specific Aim 3: Demonstrate that the changes in maternal and fetal EV proteome profiles (baseline to 2nd-3rd trimester) correlate with the changes in inflammatory and angiogenic imbalance profiles associated with PE, and with other clinical outcomes such as Preterm Birth (PTB) and Fetal Growth Restriction (FGR).

Conditions

• Preeclampsia

Timeline

• Start date: 2024-07-02
• Primary completion: 2028-09-01
• Completion: 2028-09-01
• First posted: 2024-02-08
• Last updated: 2025-12-29

Locations

1 site across 1 country: United States