Prenatal Aspirin and Postpartum Vascular Function

NCT05653973 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 202203433
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Preeclampsia is a pregnancy disorder affecting \~5-10% of pregnancies in the United States. 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 blood vessel damage and increased inflammation that occurs during the preeclamptic pregnancy and persists postpartum. Low dose aspirin (LDA; 75-150mg/daily) is currently the most effective and clinically accepted therapy for reducing preeclampsia prevalence in women at high risk for developing the syndrome. The purpose of this study is to interrogate the mechanisms by which LDA therapy mitigates persistent vascular dysfunction in postpartum women who have had preeclampsia. 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) they examine the blood vessels in a dime-sized area of the skin in women who have had a history of preeclampsia. As a compliment to these measurements, they also draw blood from the subjects and isolate the inflammatory cells.

Conditions

Preeclampsia; Microvascular Function

Outcome Measures

Primary Outcomes (2)

• microvascular endothelial function

  cutaneous vascular vasodilator response to exogenous acetylcholine perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of acetylcholine alone or co-infused with L-NAME

  at the study visit, an average of 4 hours

• microvascular endothelin-1-mediated constriction

  cutaneous vascular response to exogenous endothelin-1 perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of endothelin-1 alone or co-infused with BQ-788 or BQ-123

  at the study visit, an average of 4 hours

Study Arms (1)

assessment of microvascular function

EXPERIMENTAL

The investigators use intradermal microdialysis to deliver acetylcholine, acetylcholine + L-NAME, endothelin-1, endothelin-1 + BQ-788, and endothelin-1 + BQ-123 to the cutaneous microvasculature.

Drug: Acetylcholine; Drug: Endothelin-1

Interventions

Acetylcholine DRUG

acetylcholine, and acetylcholine + L-NAME (Nitric oxide synthase inhibitor) are locally and acutely delivered to the cutaneous microvasculature to assess endothelium- and nitric oxide-dependent dilation

assessment of microvascular function

Endothelin-1 DRUG

endothelin-1, endothelin-1 + BQ-788 (endothelin receptor type B-inhibitor), and endothelin-1 + BQ-123 (endothelin receptor type A-inhibitor) are locally and acutely delivered to the cutaneous microvasculature to assess endothelin-mediated constriction and the role of the receptor subtypes in this response.

assessment of microvascular function

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• years or older,
• weeks to 5 years postpartum
• and one of the following:
• women who had a normal pregnancy and did not use low does aspirin (LDA) during pregnancy,
• women who had a normal pregnancy and used LDA during pregnancy,
• women who had preeclampsia and did not use LDA during pregnancy,
• women who had preeclampsia and used LDA during pregnancy.

You may not qualify if:

• current daily aspirin use,
• skin diseases,
• current tobacco use,
• diagnosed or suspected hepatic or metabolic disease including chronic kidney disease (CKD) defined as reduced eGFR \< 60 mL/min/1.73m2,
• statin or other cholesterol-lowering medication,
• current antihypertensive medication,
• history of hypertension prior to pregnancy,
• history of gestational diabetes,
• current pregnancy,
• body mass index \<18.5 kg/m2,
• allergy to materials used during the experiment.(e.g. latex),
• known allergies to study drugs.

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

Acetylcholine; Endothelin-1

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biogenic Amines; Amines; Organic Chemicals; Endothelins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Central Study Contacts

Anna Reid-Stanhewicz, PHD

CONTACT

319-467-1732; anna-stanhewicz@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 7, 2022
• First Posted: December 16, 2022
• Study Start: January 3, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): July 30, 2027
• Last Updated: May 31, 2025

Record last verified: 2025-05

Locations

US (1)