Balance of Angiotensin II Receptors in Vessel Function After Preeclampsia

NCT06157580 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 202309383
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Otherwise healthy women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life. The reason why this occurs is unclear but may be related to impaired endothelial function and dysregulation of the angiotensin system that occurs during preeclampsia 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 differences in the microvascular balance of angiotensin II receptors women who have had preeclampsia. This will help the investigators better understand the mechanisms of dysregulated angiotensin II receptors in formerly preeclamptic women, and how activation or inhibition 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

Keywords

postpartum; vascular

Outcome Measures

Primary Outcomes (2)

• Change in microvascular angiotensin II (ang II) type 2 receptor (AT2R)-mediated dilation response measured by laser-Doppler flowmetry

  cutaneous vascular vasodilator responses to compound 21 perfusion in lactated Ringer's and losartan treated microdialysis sites

  at the study visit, an average of 4 hours

• Change in microvascular ang II-mediated constriction response measured by laser-Doppler flowmetry

  cutaneous vascular vasoconstrictor responses to angiotensin II perfusion in lactated Ringer's and PD-123319 treated microdialysis sites

  at the study visit, an average of 4 hours

Study Arms (2)

History of a preeclampsia

OTHER

Women who had preeclampsia in their most recent pregnancy

Drug: Compound 21; Drug: Angiotensin II

History of a healthy pregnancy

OTHER

Women who had an uncomplicated pregnancy

Drug: Compound 21; Drug: Angiotensin II

Interventions

Compound 21 DRUG

differences in vasodilation to compound 21 in the skin between groups

History of a healthy pregnancy; History of a preeclampsia

Angiotensin II DRUG

differences in vasoconstriction to angiotensin II in the skin between groups

History of a healthy pregnancy; History of a preeclampsia

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 or gestational hypertension
• 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 or \>30 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

Location

MeSH Terms

Conditions

Pre-Eclampsia

Interventions

compound 21; Angiotensin II

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Angiotensins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autacoids; Inflammation Mediators; Biological Factors

Study Design

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

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: December 6, 2023
• Study Start: December 8, 2023
• Primary Completion: October 24, 2024
• Study Completion: December 10, 2024
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)