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临床试验/NCT03493802
NCT03493802已完成不适用

Assessment of Longitudinal Changes in Endothelial Function and Oxidative Stress in Normotensive Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) - A Pilot Study

Mayo Clinic1 个研究点 分布在 1 个国家目标入组 18 人开始时间: 2017年11月1日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
发起方
Mayo Clinic
入组人数
18
试验地点
1
主要终点
Mitochondrial DNA copy number

研究概览

简要总结

The purpose of this study is to determine whether patients with autosomal dominant polycystic kidney disease (ADPKD) present with abnormal endothelial function, increased levels of NOX4 activity and mitochondrial abnormalities, contributing to oxidative stress from early stages that correlate with disease severity.

详细描述

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic and the fourth cause of end-stage renal disease (ESRD) in adults worldwide. Cardiovascular diseases are the most important non-cystic complications and continue to be the leading cause of premature mortality in these patients. Hypertension (HTN) is present in approximately 50% of the patients at early stages, and increases to nearly 100% at ESRD. Furthermore, HTN contributes to the underlying renal disease progression. Nitric oxide (NO) associated endothelium-dependent vasorelaxation has been shown to be impaired in small subcutaneous resistance vessels from patients with ADPKD before the development of HTN. However, the principal contributors to vascular dysfunction remain unclear.

The investigators broad objective is to evaluate the presence and extent of endothelial dysfunction and its association with oxidative stress in young normotensive patients with ADPKD, with the long term goal of timely intervention to slow the progression of the disease in these patients.

Participants in this study will have their endothelial function assessed using a non-invasive technique, peripheral arterial tonometry (PAT), which has been shown to be a useful, highly reproducible, and non-operator dependent method for non-invasive assessment of vascular health. The investigators will assess longitudinal changes in endothelial function using PAT with the intention of establishing if this methodology offers the potential of non-invasive measures of early vascular disease in young normotensive patients with ADPKD. Biochemical markers of endothelial dysfunction will be assessed concomitantly. In addition, the investigators will assess oxidative stress levels in these patients, with the intention of determining the association with endothelial dysfunction.

研究设计

研究类型
Observational
观察模型
Case Control
时间视角
Prospective

入排标准

年龄范围
18 Years 至 40 Years(Adult)
性别
All
接受健康志愿者

入选标准

  • ADPKD Patients:
  • ADPKD (based on Ravine et al. criteria)
  • Class 1 B-D according to our imaging classification
  • Male and female subjects 18 - 40 years of age, inclusive
  • Estimated GFR> 60 mL/min/m2 (CKD-Epi equation)
  • Systolic BP≤130mmHg without taking HTN medications
  • Ability to provide written, informed consent
  • Healthy controls:
  • Male and female subjects 18 - 40 years of age, inclusive
  • estimated GFR> 60 mL/min/m2 (CKD-EPI equation)
  • Systolic BP≤130mmHg without taking HTN medications
  • Ability to provide written, informed consent

排除标准

  • ADPKD Patients:
  • Class 2 according to our imaging classification
  • Concomitant systemic disease in the kidney (e.g. lupus, hepatitis B or C, amyloidosis)
  • Diabetes mellitus (fasting glucose > 126 mg/dL or treatment with insulin or oral hypoglycemics).
  • Predicted urine protein excretion in urinalysis >1 g/24 hrs
  • Abnormal urinalysis suggestive of concomitant glomerular disease
  • Subjects having contraindications to, or interference with MRI assessments. [For example: ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large abdominal/back tattoos, etc].
  • Female subjects that are pregnant
  • Healthy controls:
  • Previous personal or family history of kidney disease
  • Concomitant systemic disease in the kidney (e.g. lupus, hepatitis B or C, amyloidosis)
  • Diabetes mellitus (fasting glucose > 126 mg/dL or treatment with insulin or oral hypoglycemics).
  • Presence of proteinuria
  • Abnormal urinalysis suggestive glomerular disease
  • Subjects having contraindications to, or interference with MRI assessments. [For example: ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large abdominal/back tattoos, etc]
  • Female subjects that are pregnant

结局指标

主要结局

Mitochondrial DNA copy number

时间窗: 18 months

Plasma and urine levels of the mitochondria encoded genes cytochrome-c oxidase-3 (COX3) and nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit-1 (ND1) determined by quantitative real-time polymerase chain reaction

Total kidney volume (TKV)

时间窗: 18 months

Determined by MRI

Renal blood flow (RBF)

时间窗: 18 months

Determined by MRI

Assessment of endothelial function by Peripheral Artery Tonometry (PAT)

时间窗: 18 months

PAT is a novel non-invasive technology which records volume changes in the microcirculation of the digits in response to hyperemia, to measure peripheral vasodilator response as a measure for endothelial dysfunction.

Glomerular filtration rate (GFR)

时间窗: 18 months

Determination of iothalamate clearance

NADPH oxidase 4 (NOX4) expression/activity

时间窗: 18 months

Determined by ELISA from plasma and urine

次要结局

未报告次要终点

研究者

发起方
Mayo Clinic
申办方类型
Other
责任方
Principal Investigator
主要研究者

Maria V. Irazabal Mira

Principal Investigator

Mayo Clinic

研究点 (1)

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