Role of ET-1, Physical Activity, and Sedentary Behavior in Microvascular Dysfunction Following GDM

NCT ID: NCT06547619

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-01
• Study Completion Date: 2027-05-31

Brief Summary

Women with a history of gestational diabetes mellitus (GDM) are at a 2-fold greater risk for the development of overt cardiovascular disease (CVD) following the effected pregnancy. While subsequent development of type II diabetes elevates this risk, prior GDM is an independent risk factor for CVD morbidity, particularly, within the first decade postpartum. GDM is associated with impaired endothelial function during pregnancy and decrements in macro- and microvascular function persist postpartum, despite the remission of insulin resistance following delivery. Collectively, while the association between GDM and elevated lifetime CVD risk is clear, and available evidence demonstrates a link between GDM and vascular dysfunction in the decade following pregnancy, the mechanisms mediating this persistent dysfunction remain unexamined.

The purpose of this investigation is to examine the role of endothelin-1, a potent vasoconstrictor, in aberrant microvascular function in otherwise healthy women with a history of GDM and to identify whether this mechanism is influenced by physical activity and sedentary behavior.

Conditions

Gestational Diabetes; Endothelial Dysfunction; Physical Inactivity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

local lactated Ringer's perfusion

lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control

Group Type: PLACEBO_COMPARATOR

Insulin aspart

Intervention Type: DRUG

insulin aspart is perfused at 5 ascending concentrations (10\^-8M - 10\^-4 M) for 10 minutes each

local BQ-788 and BQ-123 perfusion

local ET-1 inhibitors perfused through the microdialysis fiber to serve as the experimental treatment

Group Type: EXPERIMENTAL

Insulin aspart

Intervention Type: DRUG

insulin aspart is perfused at 5 ascending concentrations (10\^-8M - 10\^-4 M) for 10 minutes each

local L-NAME perfusion

local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase

Group Type: EXPERIMENTAL

Insulin aspart

Intervention Type: DRUG

insulin aspart is perfused at 5 ascending concentrations (10\^-8M - 10\^-4 M) for 10 minutes each

local BQ-788 + BQ-123 + L-NAME perfusion

local ET-1 inhibitors and L-NAME are perfused through the microdialysis fiber to inhibit nitric oxide synthase during the experimental treatment

Group Type: EXPERIMENTAL

Insulin aspart

Intervention Type: DRUG

insulin aspart is perfused at 5 ascending concentrations (10\^-8M - 10\^-4 M) for 10 minutes each

Interventions

Insulin aspart

insulin aspart is perfused at 5 ascending concentrations (10\^-8M - 10\^-4 M) for 10 minutes each

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• history of pregnancy within 5 years of the study visit
• had healthy pregnancy OR had gestational diabetes diagnosed by their obstetrician and confirmed according to the American College of Obstetricians and Gynecologists criteria for gestational diabetes.

Exclusion Criteria

• skin diseases,
• current tobacco or electronic cigarette/vape pen use,
• diagnosed or suspected hepatic or metabolic disease including diabetes,
• statin or other cholesterol-lowering medication,
• current antihypertensive medication,
• history of preeclampsia or gestational hypertension
• current hypertension,
• current pregnancy,
• body mass index <18.5 kg/m2,
• allergy to materials used during the experiment.(e.g. latex), known allergies to study drugs.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Anna Stanhewicz, PhD

OTHER

Sponsor Role: lead

Responsible Party

Anna Stanhewicz, PhD

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

University of Iowa

Iowa City, Iowa, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Anna Reid-Stanhewicz, PHD

Role: CONTACT

anna-stanhewicz@uiowa.edu

319-467-1732

Facility Contacts

Anna Stanhewicz, PhD

Role: primary

anna-stanhewicz@uiowa.edu

319-467-1732

Other Identifiers

202405270

Identifier Type: -

Identifier Source: org_study_id