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临床试验/NCT05946798
NCT05946798进行中(未招募)1 期

Role of NADPH Oxidase in Microvascular Dysfunction Following GDM

Anna Stanhewicz, PhD1 个研究点 分布在 1 个国家目标入组 40 人开始时间: 2023年8月30日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
进行中(未招募)
发起方
入组人数
40
试验地点
1
主要终点
microvascular acetylcholine-mediated dilation

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Parallel
主要目的
Basic Science
盲法
None

入排标准

年龄范围
18 Years 至 50 Years(Adult)
性别
Female
接受健康志愿者

入选标准

  • 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

排除标准

  • 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

研究组 & 干预措施

local apocynin perfusion

Experimental

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

干预措施: Insulin aspart (Drug)

local apocynin perfusion

Experimental

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

干预措施: Acetylcholine (Drug)

local lactated Ringer's perfusion

Placebo Comparator

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

干预措施: Acetylcholine (Drug)

local lactated Ringer's perfusion

Placebo Comparator

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

干预措施: Insulin aspart (Drug)

local L-NAME perfusion

Experimental

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

干预措施: Acetylcholine (Drug)

local apocynin + L-NAME perfusion

Experimental

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

干预措施: Insulin aspart (Drug)

local apocynin + L-NAME perfusion

Experimental

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

干预措施: Acetylcholine (Drug)

local L-NAME perfusion

Experimental

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

干预措施: Insulin aspart (Drug)

结局指标

主要结局

microvascular acetylcholine-mediated dilation

时间窗: 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

时间窗: 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

次要结局

  • endothelial cell NADPH oxidase expression(at the study visit, an average of 4 hours)

研究者

发起方
Anna Stanhewicz, PhD
申办方类型
Other
责任方
Sponsor Investigator
主要研究者

Anna Stanhewicz, PhD

Assistant Professor

University of Iowa

研究点 (1)

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