Mechanisms of Pregnancy Vascular Adaptations

Vascular Diseases Clinical Trial

Official title:

Angiotensin 2 Receptor (AT2R) Expression/Activation in Endothelial Cells in Preeclampsia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03806283
• Other study ID #: Meriter IRB 2018-006
• Secondary ID: 5R01HL134779-02A
• Status: Recruiting
• Start date: November 20, 2018
• Est. completion date: April 2027

Study information

• Verified date: October 2023
• Source: University of Wisconsin, Madison
• Contact: Sharon E Blohowiak, MS
• Phone: 6084176957
• Email: sblohowiak[@]wisc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: April 2027
• Est. primary completion date: April 2027
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Eclampsia
• Pre-Eclampsia
• Vascular Diseases

Intervention

Procedure:
• Omental Biopsy
The surgeon and clinical care team will conduct the c-section to deliver the baby and the placenta as clinically indicated. After delivery, during the closing procedures, the surgeon will indicate a time for a participating Ob/Gyn physician on the study team to collect the omental bio-specimen. Omentum is frequently excised or removed for clinical reasons during surgical procedures. Omentum has small blood vessels within it that have been used for evaluation of vascular functional changes in research. The investigators wish to isolate one to three vessels of 5 to 7 cm length. The surgeon will then close and the clinical care team will resume their standard of care activities.

Locations

Country	Name	City	State
United States	UnityPoint Health-Meriter Hospital	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantify the vascular AT2R expression and vascular function in placental and omental vascular arteries in both preeclamptic and controlled pregnancies.	The researchers will measure the amount and distribution of vascular angiotensin II type 1 receptor (AT1R) and AT2R during normal human pregnancy and in preeclampsia. The researchers will assess if AT2R expression varies with severity of preeclampsia. Based on pilot data, the researchers expect decreased AT2R and increased AT1R protein levels in preeclamptic vs normotensive vessels.	1 year
Primary	To test if ex-vivo treatment of AT2R agonists reverses the endothelial dysfunction and improves vasoconstriction in the preeclamptic vessels.	The researchers will quantify vascular AT2R expression and vascular function in placental and omental arteries of preeclamptic vs normal pregnant women. Vascular function studies will also test if ex vivo treatment with AT2R agonist reverses endothelial dysfunction and vasoconstriction in preeclamptic vessels.	1 year
Primary	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.	To test the AT2R-mediated mechanisms, endothelium-derived hyperpolarizing factor (EDHF), nitric oxide, and prostacyclin (PGI2) pathways of vascular relaxation and AT1R-mediated vasoconstrictor pathways will be determined. Also, the expression of endothelial nitric oxide synthase, its activity state, and signaling components of EDHF and PGI2 pathways, as well as nitrate/nitrite and PGI2 production and changes in membrane potential, will be measured	1 year