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临床试验/NCT02365285
NCT02365285已完成1 期

Racial Differences in Vagal Control of Glucose Homeostasis

Vanderbilt University Medical Center1 个研究点 分布在 1 个国家目标入组 23 人开始时间: 2015年3月最近更新:
适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
已完成
入组人数
23
试验地点
1
主要终点
Change in Oxidative Stress: Baseline to 2 Hours

研究概览

简要总结

The investigators will test the hypothesis that acute central acetylcholinesterase inhibition will restore PNS activity and reduce oxidation in AAW compared to whites.

详细描述

Obesity has a greater detrimental impact on the health of African American women (AAW) than on any other racial or gender group. Nearly 80% of AAW are overweight or obese. Reduced insulin sensitivity is more prevalent among AAW as compared to white women and men of both races. This condition puts AAW at increased risk for the development of type 2 diabetes mellitus. The exact mechanism underlying these pathophysiological differences remains unknown. The investigators have found that obese AAW have decreased parasympathetic nerve (PNS) activity compared to whites and recent studies in animal models showed that the PNS confers protection against oxidative stress. In our AA cohort, PNS activity was directly correlated with insulin sensitivity in obese AAW even after controlling for differences in age, blood pressure and visceral adiposity. Equally important, the investigators also showed that the decrease in insulin sensitivity was associated with increased oxidative stress as measured by plasma levels of F2-isoprostanes. Taken together these findings lead us to hypothesize that the decreased PNS activity in obese AAW compared to white women has deleterious effects on oxidative stress and insulin sensitivity.The investigators will test the hypothesis that acute central acetylcholinesterase inhibition will restore PNS activity and reduce oxidation in AAW compared to whites.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Crossover
主要目的
Treatment
盲法
Double (Participant, Investigator)

入排标准

年龄范围
18 Years 至 60 Years(Adult)
性别
Female
接受健康志愿者

入选标准

  • African American or white (race will be self-defined, but only subjects who report both parents of the same race will be included)
  • 18-60 years old
  • BMI 30-45 Kg/m2
  • Not pregnant or breastfeeding

排除标准

  • Pregnant or breastfeeding
  • Diabetes diagnosis (defined by the American Diabetes Association (ADA) criteria)38
  • Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy.
  • Arrhythmia (first-, second-, and third-degree atrioventricular (AV) block)
  • Significant weight change >5% in the past 3 months
  • Impaired hepatic function (AST and/or Alanine transaminase (ALT) > one and one half times (1.5X) upper limit of normal range)
  • Impaired renal function (eGFR <60ml/min)
  • Users of strong inhibitors of Cytochrome P450 3A4 (CYP3A4) or cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6)
  • Users of other acetylcholinesterase inhibitors such as pyridostigmine or bethanechol
  • History of alcohol or drug abuse
  • Mental conditions rendering the subject unable to understand the nature, scope, and possible consequences of the study
  • Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

研究组 & 干预措施

Galantamine 16 mg then placebo

Experimental

Galantamine 16 mg po one time dose then placebo on 2nd visit

干预措施: Galantamine (Drug)

Galantamine 16 mg then placebo

Experimental

Galantamine 16 mg po one time dose then placebo on 2nd visit

干预措施: Placebo Oral Capsule (Drug)

Galantamine 16 mg then placebo

Experimental

Galantamine 16 mg po one time dose then placebo on 2nd visit

干预措施: Intralipid (Drug)

Galantamine 16 mg then placebo

Experimental

Galantamine 16 mg po one time dose then placebo on 2nd visit

干预措施: Heparin (Drug)

Placebo then Galantamine 16 mg

Placebo Comparator

Placebo capsule po one time dose then Galantamine 16 mg on 2nd visit

干预措施: Galantamine (Drug)

Placebo then Galantamine 16 mg

Placebo Comparator

Placebo capsule po one time dose then Galantamine 16 mg on 2nd visit

干预措施: Placebo Oral Capsule (Drug)

Placebo then Galantamine 16 mg

Placebo Comparator

Placebo capsule po one time dose then Galantamine 16 mg on 2nd visit

干预措施: Intralipid (Drug)

Placebo then Galantamine 16 mg

Placebo Comparator

Placebo capsule po one time dose then Galantamine 16 mg on 2nd visit

干预措施: Heparin (Drug)

结局指标

主要结局

Change in Oxidative Stress: Baseline to 2 Hours

时间窗: Baseline to 2 hours

Measure F-2 isoprostanes as a marker of oxidation

Change in Oxidative Stress: Baseline to 4 Hours

时间窗: Baseline to 4 hours

Measure F-2 isoprostanes as a marker of oxidation

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Cyndya Shibao

Medical Doctor, Assistant Professor of Medicine

Vanderbilt University

研究点 (1)

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