Clinical trial NCT04632589: Losartan for Improved Vascular Endothelial Function After Preeclampsia
Official title: Angiotensin II Receptor Inhibition to Improve Microvascular Function in Women Who Have Had Preeclampsia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Preeclampsia Postpartum
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2020-11-17
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life, even if they are otherwise healthy. The reason why this occurs is unclear but may be related to blood vessel damage and increased inflammation that occurs during the preeclamptic pregnancy and persists postpartum. The purpose of this investigation is to determine the mechanisms contributing to this lasting blood vessel damage and to test whether taking a medication that blocks angiotensin II receptors (losartan) decrease these negative effects in women who have had preeclampsia. Identification of these mechanisms and treatment strategies may lead to better clinical management,of cardiovascular disease risk in these women.

In this study we use the blood vessels in the skin as a representative vascular bed. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) we examine the blood vessels in a nickle-sized area of the skin in women who have had preeclampsia. We make these measurements after the subjects take a placebo and after they take losartan (an angiotensin II receptor blocker) to test whether this treatment improves vascular function in these women. As a compliment to these measurements, we also draw blood from the subjects and isolate the inflammatory cells to test how sensitive their inflammatory responses are following the placebo and the losartan treatment.


Eligibility criteria: Inclusion Criteria:

Post-partum women,

* 18 years or older,
* who have delivered within 24 months of the study visit
* who have had a preeclamptic pregnancy diagnosed by their obstetrician and confirmed according to the American College of Obstetricians and Gynecologists criteria for preeclampsia. \[This information will be self-reported by the subjects.\]
* Using an effective method of birth control and not planning to become pregnant in the next 6 months.

Exclusion Criteria:

* skin diseases,
* current tobacco use,
* diagnosed or suspected hepatic or metabolic disease including chronic kidney disease (CKD) defined as reduced eGFR \< 60 mL/min/1.73m2,
* statin or other cholesterol-lowering medication,
* current antihypertensive medication,
* history of hypertension prior to pregnancy,
* history of gestational diabetes,
* current pregnancy or breastfeeding,
* body mass index \<18.5 kg/m2,
* allergy to materials used during the experiment.(e.g. latex),
* known allergies to study drugs.

Primary outcomes:
measure: Microvascular endothelial function following systemic AT1 receptor inhibition
timeFrame: at the completion of 6 weeks of oral losartan treatment
measure: Microvascular endothelial function following placebo
timeFrame: at the completion of 6 weeks of placebo treatment
measure: Microvascular angiotensin II sensitivity following systemic AT1 receptor inhibition
timeFrame: at the completion of 6 weeks of oral losartan treatment, and 2) at the completion of 6 weeks of placebo treatment
measure: Microvascular angiotensin II sensitivity following placebo
timeFrame: at the completion of 6 weeks of placebo treatment
measure: Central and Peripheral Vascular Stiffness following systemic AT1 receptor inhibition
timeFrame: at the completion of 6 weeks of oral losartan treatment
measure: Central and Peripheral Vascular Stiffness following placebo
timeFrame: at the completion of 6 weeks of placebo treatment
Secondary outcomes:
measure: circulating inflammatory cytokines
timeFrame: a total of 2 times throughout the study: 1) at the completion of 6 weeks of oral losartan treatment, and 2) at the completion of 6 weeks of placebo treatment
measure: PBMC inflammatory sensitivity
timeFrame: a total of 2 times throughout the study: 1) at the completion of 6 weeks of oral losartan treatment, and 2) at the completion of 6 weeks of placebo treatment
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
Study officials:
affiliation: University of Iowa
name: Anna Stanhewicz, PhD
role: PRINCIPAL_INVESTIGATOR
References: