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

Early Phase 1

Recruiting

• Conditions: Gestational Diabetes; Endothelial Dysfunction; Physical Inactivity
• Interventions: Drug: Insulin aspart

• Registration Number: NCT06547619
• Lead Sponsor: Anna Stanhewicz, PhD

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-08-07
• Study First Submitted QC: 2024-08-07
• Study First Posted: 2024-08-09
• Study Start: 2024-10-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-25
• Last Update Posted: 2024-11-26
• Primary Completion: 2026-05
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
local lactated Ringer's perfusion	Insulin aspart	lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control
local BQ-788 and BQ-123 perfusion	Insulin aspart	local ET-1 inhibitors perfused through the microdialysis fiber to serve as the experimental treatment
local BQ-788 + BQ-123 + L-NAME perfusion	Insulin aspart	local ET-1 inhibitors and L-NAME are perfused through the microdialysis fiber to inhibit nitric oxide synthase during the experimental treatment
local L-NAME perfusion	Insulin aspart	local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase

Primary Outcome Measures

Name	Time	Method
amount of microvascular insulin-mediated dilation	at the study visit, an average of 4 hours	cutaneous vascular vasodilator responses to insulin perfusion in lactated Ringer's, BQ 788 and BQ-123, and L-NAME treated microdialysis sites

Trial Locations

Locations (1)

University of Iowa; 🇺🇸 Iowa City, Iowa, United States