Vascular Effects of High-Salt After Preeclampsia

NCT06749418 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 202408643
• Study Type: interventional
• Target: 40
• 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. Importantly, women who had preeclampsia have an exaggerated vascular responsiveness to hypertensive stimuli, such as high-salt intake, compared to women who had a healthy pregnancy. 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. While the association between a history of preeclampsia and vascular dysfunction leading to elevated CVD risk is well known, the mechanisms underlying this dysfunction remains unclear. The purpose of this study is to examine the role of vascular mineralocorticoid receptor, the terminal receptor in the angiotensin system that contributes to blood pressure regulation, in mediating exaggerated microvascular endothelial dysfunction before and after a high-salt stimulus. This will help us better understand the mechanisms of microvascular dysfunction these women, and how inhibition of these receptors may improve microvascular function. In this study, we 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) we examine the blood vessels in a nickel-sized area of the skin.

Conditions

Preeclampsia; Preeclampsia Postpartum

Outcome Measures

Primary Outcomes (2)

• Change in microvascular endothelial function following local eplerenone 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 eplerenone compared to control (Ringer's solution), followed by L-NAME infusion to quantify NO-dependent response

  Day 3 (low-salt diet run in) and Day 10 (low-salt diet + high-salt supplement)

• Changes in 24-hour urine sodium

  The investigators will measure urine sodium to ensure differences in salt-take between low- and high-salt.

  Day 2, Day 9

Secondary Outcomes (3)

• Changes in circulating aldosterone concentrations

  Day 3, Day 10

• Changes in circulating angiotensin II concentrations

  Day 3, Day 10

• Changes in ambulatory blood pressure

  Day 2, Day 9

Study Arms (1)

High-salt supplement

EXPERIMENTAL

Participants will be counseled to consume a low-salt diet (\<2000 mg/day of sodium) for 10 days. After 3 days of a low-salt diet, participants will consume the high-salt supplement (4500 mg/day) for 7 days while maintaining a low-salt diet. On days 3 and 10, participants will arrive at the laboratory where the investigators will assess microvascular endothelial function. Blood will be collected to investigate circulating angiotensin II responses to low- (day 3) and high- (day 10) salt diet. On days 2 and 9, participants will undergo ambulatory blood pressure monitoring and 24-hour urine collection.

Drug: Eplerenone

Interventions

Eplerenone DRUG

Local heating: eplerenone 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.

High-salt supplement

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
• history of gestational hypertension without preeclampsia
• skin diseases
• current tobacco use
• current antihypertensive medication
• statin or other cholesterol-lowering medication
• currently 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 or salt-supplement

Sponsors & Collaborators

• Anna Stanhewicz, PhD: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Pre-Eclampsia

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Anna Reid-Stanhewicz, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelsey Schwartz, PhD

CONTACT

319-467-1732; 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: December 19, 2024
• First Posted: December 27, 2024
• Study Start: January 2, 2025
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): November 15, 2027
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)