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Role of NADPH Oxidase in Microvascular Dysfunction Following GDM

Primary Purpose

Gestational Diabetes, Oxidative Stress, Vascular Endothelial Function

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Acetylcholine
Insulin aspart
Sponsored by
Anna Stanhewicz, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Gestational Diabetes focused on measuring gestational diabetes, postpartum, vascular

Eligibility Criteria

18 Years - 50 Years (Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

  • University of IowaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

local lactated Ringer's perfusion

local apocynin perfusion

local L-NAME perfusion

local apocynin + L-NAME perfusion

Arm Description

lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control

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

local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase

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

Outcomes

Primary Outcome Measures

microvascular acetylcholine-mediated dilation
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
cutaneous vascular vasodilator responses to insulin perfusion in lactated Ringer's, apocynin, L-NAME, and apocynin+L-NAME treated microdialysis sites

Secondary Outcome Measures

endothelial cell NADPH oxidase expression
NADPH oxidase expression in biopsied endothelial cells

Full Information

First Posted
June 29, 2023
Last Updated
September 13, 2023
Sponsor
Anna Stanhewicz, PhD
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1. Study Identification

Unique Protocol Identification Number
NCT05946798
Brief Title
Role of NADPH Oxidase in Microvascular Dysfunction Following GDM
Official Title
Role of NADPH Oxidase in Microvascular Dysfunction Following GDM
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 30, 2023 (Actual)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
June 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Anna Stanhewicz, PhD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gestational Diabetes, Oxidative Stress, Vascular Endothelial Function
Keywords
gestational diabetes, postpartum, vascular

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
local lactated Ringer's perfusion
Arm Type
Placebo Comparator
Arm Description
lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control
Arm Title
local apocynin perfusion
Arm Type
Experimental
Arm Description
local apocynin is perfused through the microdialysis fiber to serve as the NADPH oxidase inhibited experimental treatment
Arm Title
local L-NAME perfusion
Arm Type
Experimental
Arm Description
local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase
Arm Title
local apocynin + L-NAME perfusion
Arm Type
Experimental
Arm Description
local apocynin and L-NAME are perfused through the microdialysis fiber for dual inhibition of NADPH oxidase and nitric oxide synthase
Intervention Type
Drug
Intervention Name(s)
Acetylcholine
Intervention Description
acetylcholine is perfused at 10 ascending concentrations (10^-10M - 10^-1 M) for 5 minutes each
Intervention Type
Drug
Intervention Name(s)
Insulin aspart
Intervention Description
insulin aspart is perfused at 5 ascending concentrations (10^-8M - 10^-4 M) for 10 minutes each
Primary Outcome Measure Information:
Title
microvascular acetylcholine-mediated dilation
Description
cutaneous vascular vasodilator responses to acetylcholine perfusion in lactated Ringer's, apocynin, L-NAME, and apocynin+L-NAME treated microdialysis sites
Time Frame
at the study visit, an average of 4 hours
Title
microvascular insulin-mediated dilation
Description
cutaneous vascular vasodilator responses to insulin perfusion in lactated Ringer's, apocynin, L-NAME, and apocynin+L-NAME treated microdialysis sites
Time Frame
at the study visit, an average of 4 hours
Secondary Outcome Measure Information:
Title
endothelial cell NADPH oxidase expression
Description
NADPH oxidase expression in biopsied endothelial cells
Time Frame
at the study visit, an average of 4 hours

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Reid-Stanhewicz, PHD
Phone
319-467-1732
Email
anna-stanhewicz@uiowa.edu
Facility Information:
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Stanhewicz, PhD
Phone
319-467-1732
Email
anna-stanhewicz@uiowa.edu

12. IPD Sharing Statement

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Role of NADPH Oxidase in Microvascular Dysfunction Following GDM

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