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Trial record 92 of 147 for:    severe preeclampsia AND hypertensive disorders

Angiotensin 2 Receptor (AT2R) in Endothelial Cells in Preeclampsia

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ClinicalTrials.gov Identifier: NCT03806283
Recruitment Status : Active, not recruiting
First Posted : January 16, 2019
Last Update Posted : January 17, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of Wisconsin, Madison

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.

Condition or disease Intervention/treatment
Pre-Eclampsia Vascular Diseases Procedure: Omental Biopsy

Detailed Description:

Trial Design: The study is a comparison of two cohorts, those with and without preeclampsia during pregnancy. The study team plans to investigate role of AT2 in modulation of vascular function/dysfunction using vessels isolated from the omental biopsies by examining 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 70 pregnant women. This is because 32 omental biopsies and 32 placentas are required to meet proposed statistical considerations. Subjects have the option of providing just one or both of the specimens. There is a possibility as few as 32 subjects could be enrolled and a maximum of 64 subjects could be enrolled to meet this requirement. There is an additional 6 subjects enrollment built into the enrollment number to allow for replacement of subjects based on lack of clinical data in some subjects, failure of tissue viability and hence experiments.

This required enrollment (32) is divided into two cohorts based on the diagnosis of preeclampsia: 16 of each type of specimen in which the woman was diagnosed with preeclampsia during her pregnancy, and 16 of each type of specimen in which the woman was not diagnosed with preeclampsia during her pregnancy. Additionally, each cohort of 16 will be divided into two groups based on gender of the fetus, 8 male fetuses and 8 female fetuses


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Study Type : Observational
Estimated Enrollment : 70 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Angiotensin 2 Receptor (AT2R) Expression/Activation in Endothelial Cells in Preeclampsia
Actual Study Start Date : November 20, 2018
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : July 1, 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Cohort 1 no Preeclampsia
Cohort 1: 16 mothers with no diagnosis of preeclampsia during pregnancy (8 male, 8 female neonate) Omental Biopsy and placental collection will be performed
Procedure: Omental Biopsy
The surgeon and clinical care team will conduct the c-section to deliver the baby and the placenta as clinically indicated. 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.

Cohort 2 mild or severe Preeclampsia
Cohort 2: 16 mothers with diagnosis of mild or severe preeclampsia during pregnancy (8 male, 8 female neonate) Omental Biopsy and placental collection will be performed
Procedure: Omental Biopsy
The surgeon and clinical care team will conduct the c-section to deliver the baby and the placenta as clinically indicated. 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.




Primary Outcome Measures :
  1. Quantify the vascular AT2R expression and vascular function in placental and omental vascular arteries in both preeclamptic and controlled pregnancies. [ Time Frame: 1 year ]
    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.

  2. To test if ex-vivo treatment of AT2R agonists reverses the endothelial dysfunction and improves vasoconstriction in the preeclamptic vessels. [ Time Frame: 1 year ]
    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.

  3. 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. [ Time Frame: 1 year ]
    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


Biospecimen Retention:   Samples Without DNA
omental tissue (research surgical excision) placental tissue (standard of care clinical delivery)


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Pregnant women with or without Preeclampsia who will be undergoing a C-section
Criteria

Inclusion Criteria:

  • female
  • Minimum age: 18
  • Maximum age: 35
  • 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.
  • Treatment with betamethasone before 36 weeks and 0 days gestation
  • Singleton gestation not within 36 weeks, 0 days and 41 weeks, 0 days gestational age at the time of enrollment (delivery)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03806283


Locations
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United States, Wisconsin
UnityPoint Health-Meriter Hospital
Madison, Wisconsin, United States, 53715
Sponsors and Collaborators
University of Wisconsin, Madison
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Dinesh Shah, MD University of Wisconsin, Madison

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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT03806283     History of Changes
Other Study ID Numbers: Meriter IRB 2018-006
5R01HL134779-02 ( U.S. NIH Grant/Contract )
First Posted: January 16, 2019    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pre-Eclampsia
Eclampsia
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pregnancy-Induced
Pregnancy Complications
Angiotensin II
Giapreza
Vasoconstrictor Agents