Prenatal Aspirin and Postpartum Vascular Function

Protective Mechanisms of Prenatal Aspirin Therapy on Maternal Vascular Dysfunction Following Preeclampsia

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.

Study Overview

• Status: Recruiting
• Conditions: Preeclampsia; Microvascular Function
• Intervention / Treatment: Drug: Acetylcholine; Drug: Endothelin-1

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Anna Reid-Stanhewicz, PHD; Phone Number: 319-467-1732; Email: anna-stanhewicz@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion:

• 18 years or older,
• 12 weeks to 5 years postpartum

• and one of the following:

  1. women who had a normal pregnancy and did not use low does aspirin (LDA) during pregnancy,
  2. women who had a normal pregnancy and used LDA during pregnancy,
  3. women who had preeclampsia and did not use LDA during pregnancy,
  4. women who had preeclampsia and used LDA during pregnancy.

Exclusion:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: assessment of microvascular function; 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; 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; Drug: Endothelin-1; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Anna Stanhewicz, PhD

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2023
• Primary Completion (Anticipated): March 31, 2025
• Study Completion (Anticipated): April 30, 2025

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 15, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Cholinergic Agents; Cholinergic Agonists; Acetylcholine
• Other Study ID Numbers: 202203433

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No