Oxidative Stress in Microvascular Dysfunction Following Gestational Diabetes

Gestational Diabetes Clinical Trial

Official title:

Role of Oxidative Stress in Microvascular Dysfunction Following Gestational Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05946785
• Other study ID #: 202009357
• Status: Recruiting
• Phase: Early Phase 1
• Start date: July 1, 2023
• Est. completion date: June 2027

Study information

• Verified date: May 2024
• Source: University of Iowa
• Contact: Anna Reid-Stanhewicz, PHD
• Phone: 319-467-1732
• Email: anna-stanhewicz[@]uiowa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this investigation is to examine the role of oxidative stress in aberrant microvascular function in otherwise healthy women with a history of GDM.

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 the role of oxidative stress in mediating vascular dysfunction in women who have had gestational diabetes. 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 markers of oxidative stress and insulin-mediated eNOS phosphorylation in these cells.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: June 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

INCLUSION CRITERIA:

• female sex
• 18 -50 years old
• pregnancy history within 5 years of the study visit
• had gestational diabetes diagnosed by their obstetrician and confirmed according to the American College of Obstetricians and Gynecologists criteria for gestational diabetes
• or without a history of gestational diabetes

EXCLUSION CRITERIA:

• skin diseases
• current tobacco/e-cigarette 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 pregnancy
• body mass index <18.5 kg/m2
• allergy to materials used during the experiment.(e.g. latex), known allergies to study drugs.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes

Intervention

Drug:
• Acetylcholine
acetylcholine is perfused at 10 ascending concentrations (10^-10M - 10^-1 M) for 5 minutes each
• insulin aspart
insulin aspart is perfused at 5 ascending concentrations (10^-8M - 10^-4 M) for 10 minutes each

Locations

Country	Name	City	State
United States	University of Iowa	Iowa City	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Anna Stanhewicz, PhD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	microvascular acetylcholine-mediated dilation	cutaneous vascular vasodilator responses to acetylcholine perfusion in lactated Ringer's, ascorbate, and L-NAME treated microdialysis sites	at the study visit, an average of 4 hours
Primary	microvascular insulin-mediated dilation	cutaneous vascular vasodilator responses to insulin perfusion in lactated Ringer's, ascorbate, and L-NAME treated microdialysis sites	at the study visit, an average of 4 hours
Secondary	endothelial cell markers of oxidative stress	nitrotyrosine, MnSOD and NADPH oxidase expression in biopsied endothelial cells	at the study visit, an average of 4 hours
Secondary	endothelial cell insulin-stimulated eNOS phosphorylation	eNOS phosphorylation response to incubation with insulin in biopsied endothelial cells	at the study visit, an average of 4 hours