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

• 批准号: 9117510
• 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
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9117510
• 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; Curcumin; Cyst; Cystic Kidney Diseases; Cystic kidney; Data; Development; Disease; Disease Progression; Double-Blind Method; Effectiveness; Endothelium; Event; Functional disorder; Future; Genetic Transcription; Goals; Growth; Health; Hereditary Disease; Human; Hypertension; 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; Placebo Control; 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; double-blind placebo controlled trial; endothelial dysfunction; improved; in vivo; insight; kidney cell; mortality; novel; patient subsets; polyphenol; prevent; public health relevance; vascular endothelial dysfunction; young adult

 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（由适用提供）：尽管通常被认为是成年人的疾病，但ADPKD的并发症始于儿童。虽然ADPKD的标志是多种肾囊肿的发展和持续增长，导致肾功能的最终丧失，但受影响患者死亡的主要原因本质上是心血管。血管功能障碍（内皮功能障碍和较大的弹性动脉僵硬）在疾病的早期很早就证明，似乎涉及增加的氧化应激和感染。预防ADPKD成人CVD的治疗选择有限，因此童年可能代表关键的治疗窗口。姜黄素是在印度香料姜黄中发现的一种安全，天然存在的多酚，具有激活关键抗氧化剂转录，抑制注射并减少增殖的独特能力。 AIM 1使用1年随机，安慰剂对照，双盲试验来评估姜黄素（25 mg/kg/day）使用ADPKD改善儿童和年轻人（6-22岁）的血管功能的效率。 AIM 2将确定（在18-22岁年龄的患者的亚组中），如果使用最先进的质谱法的状态与氧化应激和炎症减少有关。第三个探索性目标将通过MRI扫描评估总肾脏量的变化。这项研究有可能建立一种新颖，安全且易于提供的治疗方法，用于治疗动脉功能障碍，并可能是肾囊性疾病，其中包括患有ADPKD的儿童和年轻人的人群。