- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05946785
Oxidative Stress in Microvascular Dysfunction Following Gestational Diabetes
Role of Oxidative Stress in Microvascular Dysfunction Following Gestational Diabetes
Study Overview
Status
Intervention / Treatment
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 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.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Anna Reid-Stanhewicz, PHD
- Phone Number: 319-467-1732
- Email: anna-stanhewicz@uiowa.edu
Study Locations
-
-
Iowa
-
Iowa City, Iowa, United States, 52242
- University of Iowa
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: local lactated Ringer's perfusion
lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control
|
acetylcholine is perfused at 10 ascending concentrations (10^-10M - 10^-1 M) for 5 minutes each
insulin aspart is perfused at 5 ascending concentrations (10^-8M - 10^-4 M) for 10 minutes each
|
Experimental: local ascorbate perfusion
local ascorbate is perfused through the microdialysis fiber to serve as the antioxidant experimental treatment
|
acetylcholine is perfused at 10 ascending concentrations (10^-10M - 10^-1 M) for 5 minutes each
insulin aspart is perfused at 5 ascending concentrations (10^-8M - 10^-4 M) for 10 minutes each
|
Experimental: local L-NAME perfusion
local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase
|
acetylcholine is perfused at 10 ascending concentrations (10^-10M - 10^-1 M) for 5 minutes each
insulin aspart is perfused at 5 ascending concentrations (10^-8M - 10^-4 M) for 10 minutes each
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
microvascular acetylcholine-mediated dilation
Time Frame: at the study visit, an average of 4 hours
|
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
|
microvascular insulin-mediated dilation
Time Frame: at the study visit, an average of 4 hours
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
endothelial cell markers of oxidative stress
Time Frame: at the study visit, an average of 4 hours
|
nitrotyrosine, MnSOD and NADPH oxidase expression in biopsied endothelial cells
|
at the study visit, an average of 4 hours
|
endothelial cell insulin-stimulated eNOS phosphorylation
Time Frame: at the study visit, an average of 4 hours
|
eNOS phosphorylation response to incubation with insulin in biopsied endothelial cells
|
at the study visit, an average of 4 hours
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Pregnancy Complications
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Diabetes Mellitus
- Diabetes, Gestational
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Cholinergic Agents
- Cholinergic Agonists
- Insulin Aspart
- Acetylcholine
Other Study ID Numbers
- 202009357
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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