Role of NADPH Oxidase in Microvascular Dysfunction Following GDM

Early Phase 1

Recruiting

• Conditions: Vascular Endothelial Function; Oxidative Stress; Gestational Diabetes
• Interventions: Drug: Acetylcholine; Drug: Insulin aspart

• Registration Number: NCT05946798
• Lead Sponsor: Anna Stanhewicz, PhD

Brief Summary

The purpose of this investigation is to examine NADPH oxidase as a source of reactive oxygen species contributing to aberrant microvascular function in otherwise healthy women with a history of GDM.

Detailed Description

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 NADPH oxidase as a source of reactive oxygen species contributing to aberrant microvascular function in otherwise healthy women with a history of GDM.

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 GDM. As a compliment to these measures, the investigators also collect endothelial cells from an antecubital vein and measure NADPH oxidase expression and markers of oxidative stress in these cells.

Study Timeline

• Study First Submitted: 2023-06-29
• Study First Submitted QC: 2023-07-07
• Study First Posted: 2023-07-14
• Study Start: 2023-08-30
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-13
• Primary Completion: 2027-06-30
• Study Completion: 2028-06-01

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 apocynin perfusion	Insulin aspart	local apocynin is perfused through the microdialysis fiber to serve as the NADPH oxidase inhibited experimental treatment
local apocynin + L-NAME perfusion	Insulin aspart	local apocynin and L-NAME are perfused through the microdialysis fiber for dual inhibition of NADPH oxidase and nitric oxide synthase
local L-NAME perfusion	Insulin aspart	local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase
local lactated Ringer's perfusion	Acetylcholine	lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control
local L-NAME perfusion	Acetylcholine	local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase
local apocynin perfusion	Acetylcholine	local apocynin is perfused through the microdialysis fiber to serve as the NADPH oxidase inhibited experimental treatment
local apocynin + L-NAME perfusion	Acetylcholine	local apocynin and L-NAME are perfused through the microdialysis fiber for dual inhibition of NADPH oxidase and nitric oxide synthase

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
endothelial cell NADPH oxidase expression	at the study visit, an average of 4 hours	NADPH oxidase expression in biopsied endothelial cells

Trial Locations

Locations (1)

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