Angiotensin II and Chronic Inflammation in Persistent Microvascular Dysfunction Following Preeclampsia

Study Overview
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Brief Summary
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Women who develop preeclampsia during pregnancy are more likely to develop 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 1) determine the mechanisms contributing to this lasting blood vessel damage and chronic inflammation, and to 2) identify factors (both physiological and pharmacological) that mitigate these negative effects in order to inform better clinical management of cardiovascular disease risk in women who have had preeclampsia.

Official Title
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Role of Angiotensin II and Chronic Inflammation in Persistent Microvascular Dysfunction Following Preeclamptic Pregnancy

Conditions
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Preeclampsia

Intervention / Treatment
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* Drug: Salsalate Oral Tablet
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-partum women who have delivered within two years and who have had a preeclamptic pregnancy diagnosed by their obstetrician before 34 weeks of gestation and confirmed according to the American College of Obstetricians and Gynecologists criteria for severe preeclampsia. [This information will be self-reported by the subjects.] Post-partum women who have delivered within two years and who have had a normal pregnancy. 18 years and older. Exclusion Criteria: skin diseases current tobacco use diagnosed or suspected hepatic or metabolic disease statin or other cholesterol-lowering medication history of hypertension prior to pregnancy history of gestational diabetes current pregnancy allergy to aspirin or NSAIDs or known allergy to materials used during the experiment (e.g. latex) renal disease, bleeding disorders and history of gastrointestinal bleeding. Known allergies to study drugs Taking blood thinners, aspirin or NSAIDS. Women who choose to breastfeed will not participate in any parts of the project that include salsalate.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo Oral Tablet<br>* Placebo oral table twice daily for 5 days prior to experimental testing<br>|
| Experimental: Salsalate<br> | Drug: Salsalate Oral Tablet<br>* 1500mg twice daily for 5 days prior to experimental testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in endothelial function following salsalate treatment compared to placebo treatment | Endothelium-dependent vasodilation assessed by reactivity to exogenous acetylcholine | a total of 2 times throughout the study (approximately 4 weeks): 1) at the completion of 5 days of oral salsalate treatment, and 2) at the completion of 5 days of placebo treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in inflammatory response to ang II compared to baseline | inflammatory cytokine release by isolated peripheral blood mononuclear cells | a total of 3 times throughout the study (approximately 4 weeks): 1) at the beginning of the study, 2) at the completion of the 5 day placebo treatment, and 3) at the completion of 5 days of oral salsalate treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preeclampsia, microvascular, inflammation, angiotensin II