Prenatal Aspirin and Postpartum Vascular Function

Anna Stanhewicz, PhD

Status and phase: Enrolling; Early Phase 1

Conditions: Microvascular Function; Preeclampsia

Treatments: Drug: Acetylcholine; Drug: Endothelin-1

Study type: Interventional

Funder types: Other

Identifiers

NCT05653973

202203433

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

assessment of microvascular function

Experimental group

Description:

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.

Treatment:

Drug: Endothelin-1

Drug: Acetylcholine