Role of NADPH Oxidase in Microvascular Dysfunction Following GDM

NCT ID: NCT05946798

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-30
• Study Completion Date: 2028-06-01

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.

Conditions

Gestational Diabetes; Oxidative Stress; Vascular Endothelial Function

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

Acetylcholine

Intervention Type: DRUG

acetylcholine is perfused at 10 ascending concentrations (10\^-10M - 10\^-1 M) for 5 minutes each

Insulin aspart

Intervention Type: DRUG

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

local apocynin perfusion

local apocynin is perfused through the microdialysis fiber to serve as the NADPH oxidase inhibited experimental treatment

Group Type: EXPERIMENTAL

Acetylcholine

Intervention Type: DRUG

acetylcholine is perfused at 10 ascending concentrations (10\^-10M - 10\^-1 M) for 5 minutes each

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

Acetylcholine

Intervention Type: DRUG

acetylcholine is perfused at 10 ascending concentrations (10\^-10M - 10\^-1 M) for 5 minutes each

Insulin aspart

Intervention Type: DRUG

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

local apocynin + L-NAME perfusion

local apocynin and L-NAME are perfused through the microdialysis fiber for dual inhibition of NADPH oxidase and nitric oxide synthase

Group Type: EXPERIMENTAL

Acetylcholine

Intervention Type: DRUG

acetylcholine is perfused at 10 ascending concentrations (10\^-10M - 10\^-1 M) for 5 minutes each

Insulin aspart

Intervention Type: DRUG

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

Interventions

Acetylcholine

acetylcholine is perfused at 10 ascending concentrations (10\^-10M - 10\^-1 M) for 5 minutes each

Intervention Type: DRUG

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

• 18 years or older
• pregnant 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 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 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

1R01HL169201-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

202303158

Identifier Type: -

Identifier Source: org_study_id