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

NCT ID: NCT06249178

Last Updated: 2025-12-29

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-07-02
• Study Completion Date: 2028-09-01

Brief 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

Keywords

Extracellular vesicles proteome profile; Aspirin treatment; Pregnancy; Preeclampsia

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

1. pregnant individuals age ≥18 years

2. enrolled ≤16 6/7 weeks of gestation based on the best obstetric estimate as defined by ACOG criteria

3. singleton live intrauterine gestation

4. Any of the following:

1. At least one of the high-risk criteria for HDP (per US Preventive Services Task Force Recommendation Statement [USPSTF]); i) any prior pregnancy complicated by Preeclampsia ii) current pregnancy complicated by chronic hypertension iii) chronic kidney disease iv) autoimmune disease (e.g., antiphospholipid syndrome, lupus) or

2. Two or more moderate-risk criteria for HDP (per USPSTF); i) nulliparity (no prior delivery at or after 20 weeks 0 days of gestation) ii) obesity (body mass index ≥30 kg/m2 at time of enrollment) iii) age ≥35 years (at time of expected estimated due date) iv) Black race v) Low income vi) Personal risk factors (previous pregnancy with low birth weight or SGA infant, previous adverse pregnancy outcome [unexplained stillbirth], placental abruption, interval >10 years between pregnancies).

vii) Pregnancy after in vitro conception viii) family history of preeclampsia ( i.e., mother or sister)

3. or participating in another clinical RCT of 81mg vs. 162mg aspirin for prevention of hypertensive disorders of pregnancy

Exclusion Criteria

1. age < 18 years,

2. involuntarily confined or detained

3. considered as having a diminished decision-making capacity

4. multifetal gestation

5. pregestational diabetes mellitus or gestational diabetes diagnosed < 20 weeks due to the impact on exosome response

6. known or suspected fetal aneuploidy or major congenital abnormality, fetal demise, or planned pregnancy termination

7. known allergy or hypersensitivity to aspirin or any medical condition where aspirin is contraindicated (e.g., peptic ulcer disease, nasal polyps, NSAID-induced asthma, gastrointestinal bleeding, G6PD deficiency, severe hepatic dysfunction, bleeding disorders)

8. plan to deliver at another center or participating in another intervention study that influences the primary outcome in this study, without prior approval

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Texas

OTHER

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Ohio State University

OTHER

Sponsor Role: lead

Responsible Party

Maged Costantine

MD, MBA, Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maged Costantine, MD, MBA

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine

Columbus, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Maged Costantine, MD, MBA

Role: CONTACT

Phone: 614-293-2222

Email: Maged.Costantine@osumc.edu

Kara Rood, MD

Role: CONTACT

Phone: 614-293-8045

Email: Kara.Rood@osumc.edu

Facility Contacts

Maged Costantine, MD, MBA

Role: primary

Kara Rood, MD

Role: backup

Other Identifiers

1R24HD113024

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2024H0050

Identifier Type: -

Identifier Source: org_study_id