Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD

姜黄素疗法治疗 ADPKD 儿童和年轻人的血管功能障碍

基本信息

批准号：
9754811
负责人：
Kristen Lynn Nowak
金额：
$ 15.13万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9754811
关键词：
Acute Adult Affect Age Age-Years American Antioxidants Aorta Arteries Ascorbic Acid Autosomal Dominant Polycystic Kidney Biological Blood Vessels Cardiovascular Diseases Cardiovascular system Carotid Arteries Cause of Death Child Childhood Conduct Clinical Trials Curcumin Cyst Cystic Kidney Diseases Cystic kidney Data Development Disease Disease Progression Double-Blind Method Double-blind trial Effectiveness Endothelium Event Functional disorder Future Genetic Diseases Genetic Transcription Goals Growth Health Human Hypertension Impairment In Vitro Inflammation Infusion procedures Kidney Kidney Diseases Life MRI Scans Magnetic Resonance Imaging Mass Spectrum Analysis Measures Mediating Methods Nature Nutraceutical Oral Oxidative Stress Patients Physiologic pulse Physiological Placebos Population Prognostic Marker Randomized Randomized Clinical Trials Renal function Research Rodent Model Spices Testing Therapeutic Tumeric Urine Vascular Diseases aged arterial stiffness brachial artery cardiovascular disorder prevention endothelial dysfunction improved in vivo insight kidney cell mortality novel patient subsets polyphenol prevent public health relevance vascular endothelial dysfunction young adult

项目摘要

DESCRIPTION (provided by applicant): Although often considered to be a disease of adults, complications of ADPKD begin in childhood. While the hallmark of ADPKD is the development and continued growth of multiple renal cysts that result in ultimate loss of kidney function, the leading cause of death among affected patients is cardiovascular in nature. Vascular dysfunction (endothelial dysfunction and large elastic artery stiffness) is evident very early in te course of the disease and appears to involve increased oxidative stress and inflammation. Treatment options to prevent CVD in adults with ADPKD are limited, thus childhood may represent a key therapeutic window. Curcumin is a safe, naturally occurring polyphenol found in the Indian spice turmeric that has a unique ability to activate transcription of key antioxidants, suppress inflammation, and reduce proliferation. Aim 1 will assess the efficacy of curcumin (25 mg/kg/day) for improving vascular function in children and young adults (6-22 years of age) with ADPKD, using a 1 year randomized, placebo-controlled, double-blind trial. Aim 2 will determine (in a sub-group of patients 18-22 years of age), if improvements are associated with reduced oxidative stress and inflammation, utilizing state of the art mass spectrometry methods. A third exploratory aim will assess changes in total kidney volume using MRI scans. This study has the potential to establish a novel, safe, and easy to deliver therapy for the treatment of arterial dysfunction, and possibly renal cystic disease, in an understudied population of children and young adults with ADPKD.

描述（由申请人提供）：虽然 ADPKD 的并发症通常被认为是成人的疾病，但 ADPKD 的标志是多发性肾囊肿的发展和持续生长，最终导致肾功能丧失，这是最主要的。受影响患者的死亡原因是心血管功能障碍（内皮功能障碍和大弹性动脉僵硬），这在病程早期就很明显，并且似乎与氧化应激和炎症增加有关。 ADPKD 成人的 CVD 是有限的，因此儿童期可能是一个关键的治疗窗口。姜黄素是印度香料姜黄中发现的一种安全、天然的多酚，具有激活关键抗氧化剂转录、抑制炎症和减少增殖的独特能力。目标 1 将使用为期 1 年的随机、安慰剂对照、双盲试验将利用最先进的质谱方法（在 18-22 岁的患者亚组中）确定改善是否与氧化应激和炎症减少有关。使用 MRI 扫描评估肾脏总量的变化这项研究有可能在未充分研究的人群中建立一种新颖、安全且易于实施的治疗动脉功能障碍以及可能的囊性肾病的疗法。患有 ADPKD 的儿童和年轻人。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Arterial stiffness and kidney disease progression in the systolic blood pressure intervention trial .

DOI：
10.5414/cn109982
发表时间：
2020-07
期刊：
Clinical nephrology
影响因子：
1.1
作者：
Nowak KL;Chonchol M;Jovanovich A;You Z;Ambrosius WT;Cho ME;Glasser S;Lash J;Simmons DL;Taylor A;Weiner D;Rastogi A;Oparil S;Supiano MA
通讯作者：
Supiano MA

Does inflammation affect outcomes in dialysis patients?

DOI：
10.1111/sdi.12686
发表时间：
2018-07-01
期刊：
SEMINARS IN DIALYSIS
影响因子：
1.6
作者：
Nowak, Kristen L.;Chonchol, Michel
通讯作者：
Chonchol, Michel

Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease.

DOI：
10.34067/kid.0000962019
发表时间：
2020-06
期刊：
Kidney360
影响因子：
0
作者：
Nowak KL;Jovanovich A;Farmer-Bailey H;Bispham N;Struemph T;Malaczewski M;Wang W;Chonchol M
通讯作者：
Chonchol M