Clinical trial NCT03806283: Mechanisms of Pregnancy Vascular Adaptations
Official title: Angiotensin 2 Receptor (AT2R) Expression/Activation in Endothelial Cells in Preeclampsia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pre-Eclampsia
Vascular Diseases
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2019-01-16
Enrollment: 114
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women with or without Preeclampsia who will be undergoing a C-section

Brief summary: The investigators will collect omental tissue (research surgical excision) and placental tissue (standard of care clinical delivery) from both preeclamptic and non-preeclamptic women during their c-section and use these samples to study the blood vessels, specifically the expression/activation of the AT2R.

Detailed description: Trial Design: The study is a comparison of two cohorts, those with and without preeclampsia during pregnancy. The team plans to investigate role of FABP4, PFAS and AT2 in modulation of vascular function/dysfunction using vessels isolated from the omental biopsies. The investigators will examine for the evidence of fetal vascular dysfunction mediated by decreased expression of AT2 in preeclampsia using vessels isolated from the placentas.

Study Population: The study will include pregnant women. The pregnant women will participate in the omental tissue collection, placenta collection, and the medical record review.

The study is expects a maximum enrollment of 114 pregnant women. This is because 52 omental biopsies and 52 placentas are required to meet proposed statistical considerations. Participants have the option of providing just one or both of the specimens. There is a possibility as few as 52 participants could be enrolled and a maximum of 104 participants could be enrolled to meet this requirement. There is an additional 10 participants enrollment built into the enrollment number to allow for replacement of subjects based on lack of clinical data in some participants, failure of tissue viability and hence experiments, and thus a maximum of 114 (104+10) participants could be enrolled.

This required enrollment (52) is divided into two cohorts based on the diagnosis of preeclampsia: 26 of each type of specimen in which the woman was diagnosed with preeclampsia during her pregnancy, and 26 of each type of specimen in which the woman was not diagnosed with preeclampsia during her pregnancy. Additionally, each cohort of 26 will be divided into two groups based on gender of the fetus, 13 male fetuses and 13 female fetuses

Eligibility criteria: Inclusion Criteria:

* female
* Minimum age: 18
* Maximum age: 40
* Singleton births
* Minimum gestational age at consent: 28 weeks, 0 days
* Maximum gestational age at consent: 41 weeks, 0 days
* Undergoing caesarean section, either planned or otherwise with or without trial of labor

Exclusion Criteria:

* Preexisting hypertension treated by antihypertensive agents during the prenatal period. This will not include treatment of severe hypertension by antihypertensive or use of magnesium sulfate after the patient is hospitalized for the diagnosis of preeclampsia.
* Any major fetal structural anomalies or aneuploidies
* Preexisting conditions like pre-gestational type I or type II diabetes mellitus, pre-pregnancy kidney disease with increased serum creatinine above 1.2 mg/dL, or other underlying blood vessel problems like systemic lupus erythematosus or other autoimmune conditions with evidence of pre-pregnancy proteinuria or hypertension.
* Undergoing cesarean section for placental abruption or bleeding complications.
* Singleton gestation not within 36 weeks, 0 days and 41 weeks, 0 days gestational age at the time of enrollment (delivery)

Primary outcomes:
measure: Quantify the vascular AT2R expression and vascular function in placental and omental vascular arteries in both preeclamptic and controlled pregnancies.
timeFrame: 1 year
measure: To test if ex-vivo treatment of AT2R agonists reverses the endothelial dysfunction and improves vasoconstriction in the preeclamptic vessels.
timeFrame: 1 year
measure: To test AT2R mediated mechanisms on endothelial derived hyperpolarizing factor, nitric oxide and prostacyclin pathway of vascular relaxation to examine AT2's role in vaso-relaxation and AT2R mediated vasoconstrictor pathway will be defined.
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Madison
country: United States
facility: UnityPoint Health-Meriter Hospital
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Sathish Kumar, PhD
role: PRINCIPAL_INVESTIGATOR
References: