Sensitivity of Angiotensin II Type II Receptors in Women Following Preeclampsia

NCT05937841 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 202303202
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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 impaired endothelial function and dysregulation of the angiotensin system that occurs during the preeclamptic pregnancy and persists postpartum, despite the remission of clinical symptoms. The purpose of this investigation is to determine the mechanisms contributing to this lasting blood vessel damage caused by reduced endothelial function in women who have had preeclampsia compared to women who had a healthy pregnancy. Identification of these mechanisms and treatment strategies may lead to better clinical management of cardiovascular disease risk in these women. The purpose of this study is to examine the microvascular differences in women who have had preeclampsia following activation of protective angiotensin receptors in the skin. This will help increase understanding of the mechanisms of angiotensin II receptors in these women, and how activation of these receptors may restore microvascular function. In this study, the investigators use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) the investigators examine the blood vessels in a dime-sized area of the skin.

Conditions

Preeclampsia Postpartum

Outcome Measures

Primary Outcomes (2)

• Change in microvascular blood flow response to local compound 21 treatment measured by laser-Doppler flowmetry

  Cutaneous vascular vasodilator response (cutaneous conductance; %max) to exogenous compound 21 perfusion; intradermal microdialysis for the local delivery of compound 21

  post 1 hour of skin perfusion

• Change in microvascular endothelial function following local C21 treatment compared to placebo treatment measured by laser-Doppler flowmetry

  Cutaneous vascular vasodilator response (cutaneous conductance; %max) to local heating of the skin; intradermal microdialysis for the local delivery of compound 21 compared to control (Ringer's solution), followed by L-NAME infusion to quantify NO-dependent response

  post 1 hour of skin perfusion

Secondary Outcomes (1)

• Angiotensin receptor expression in endothelial cells

  a total of 1 time during the study, within ~4 weeks following enrollment

Study Arms (1)

assessment of microvascular function

EXPERIMENTAL

The investigators use intradermal microdialysis to deliver compound 21 and L-NAME to the cutaneous microvasculature

Drug: Compound 21

Interventions

Compound 21 DRUG

AT2R sensitivity: compound 21, and compound 21+ L-NAME (nitric oxide synthase inhibitor) are locally and acutely delivered to the cutaneous microvasculature to assess AT2R-mediated dilation and role of nitric oxide in this response Local heating: compound 21 is locally and acutely delivered to the cutaneous microvasculature during local heating of the skin to assess endothelium-dependent dilation, L-NAME is added to assess nitric oxide-dependent dilation during this response

assessment of microvascular function

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• women who had preeclampsia and women who did not have preeclampsia
• weeks to 5 years postpartum
• years old

You may not qualify if:

• history of hypertension or metabolic disease before pregnancy
• history of gestational diabetes
• skin diseases
• current tobacco use
• current antihypertensive medication
• statin or other cholesterol-lowering medication
• currently pregnant or planning to become pregnant
• body mass index less than 18.5 kg/m2
• allergy to materials used during the experiment.(e.g. latex),
• known allergy to study drugs

Sponsors & Collaborators

• Anna Stanhewicz, PhD: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Related Publications (1)

• Schwartz KS, Sun M, Jalal DI, Santillan MK, Stanhewicz AE. Reduced AT2R Signaling Contributes to Endothelial Dysfunction After Preeclampsia. Hypertension. 2025 May;82(5):904-913. doi: 10.1161/HYPERTENSIONAHA.124.24098. Epub 2024 Dec 26.

  PMID: 39723536 DERIVED

MeSH Terms

Interventions

compound 21

Study Officials

• Anna Reid-Stanhewicz, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelsey Schwartz

CONTACT

319-467-3096; kelsey-schwartz@uiowa.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 21, 2023
• First Posted: July 10, 2023
• Study Start: June 28, 2023
• Primary Completion: August 12, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)