Angiotensin II and Chronic Inflammation in Persistent Microvascular Dysfunction Following Preeclampsia

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

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.

Study Overview

• Status: Completed
• Conditions: Preeclampsia
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Salsalate Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Pennsylvania
    • University Park, Pennsylvania, United States, 16802
      • Pennsylvania State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo Oral Tablet; Placebo oral table twice daily for 4 days prior to experimental testing
Experimental: Salsalate	Drug: Salsalate Oral Tablet; 1500mg twice daily for 4 days prior to experimental testing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microvascular Endothelial Function (Cutaneous Conductance, %Maximum)	Endothelium-dependent vasodilation assessed as cutaneous conductance response (cutaneous conductance = local red blood cell flux/mean arterial pressure; %maximum) to exogenous acetylcholine delivered via intradermal microdialysis.	immediately following the 4 days or oral treatment (salsalate or placebo)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral Blood Mononuclear Cell Inflammatory Response to Ang II	inflammatory cytokine (TNFalpha) release by peripheral blood mononuclear cells isolated from fresh whole blood collected via venipuncture and stimulated with angiotensin II ex vivo.	at the completion of 4 days of oral (placebo or salsalate) treatment

Collaborators and Investigators

• Sponsor: University of Iowa
• Collaborators: Penn State University
• Investigators: Principal Investigator: Anna Stanhewicz, PhD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2018
• Primary Completion (Actual): July 11, 2019
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: March 15, 2018
• First Submitted That Met QC Criteria: March 22, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: June 2, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: inflammation; preeclampsia; angiotensin II; microvascular
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Inflammation; Physiological Effects of Drugs; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Salicylsalicylic acid
• Other Study ID Numbers: 201909818

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data will be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No