Clinical trial

Sensitivity of Angiotensin II Type II Receptors in Women Following Preeclampsia

Name

202303202

Description

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.

Trial arms

Trial start

2023-06-28

Estimated PCD

2025-06-01

Trial end

2025-06-01

Status

Recruiting

Phase

Early phase I

Treatment

Compound 21

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

Arms:

assessment of microvascular function

Size

Primary endpoint

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

post 1 hour of skin perfusion

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

post 1 hour of skin perfusion

Eligibility criteria

Inclusion Criteria: * women who had preeclampsia and women who did not have preeclampsia * 12 weeks to 5 years postpartum * 18-45 years old Exclusion Criteria: * 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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 30, 'type': 'ESTIMATED'}}

Updated at

2023-07-10

1 organization

1 product

1 indication

Organization

Anna Stanhewicz

Product

Compound 21

Indication

Preeclampsia