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

 描述(申请人提供)：虽然ADPKD通常被认为是一种成年人的疾病，但ADPKD的并发症始于童年。虽然ADPKD的特点是多发性肾囊肿的发展和持续生长导致最终的肾功能丧失，但受影响患者的主要死亡原因本质上是心血管疾病。血管功能障碍(内皮功能障碍和大的弹性动脉僵硬)在疾病的早期就很明显，似乎涉及氧化应激和炎症的增加。预防成人ADPKD患者心血管疾病的治疗选择有限，因此童年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、自然存在的多酚，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。目的1采用为期1年的随机、安慰剂对照、双盲试验，评价姜黄素(25 mg/kg/d)改善ADPKD儿童和青壮年(6-22岁)血管功能的疗效。目标2将利用最先进的质谱学方法，确定(在18-22岁的一组患者中)改善是否与减少氧化应激和炎症有关。第三个探索性目标将使用MRI扫描来评估总肾脏体积的变化。这项研究有可能建立一种新的、安全的、易于提供的治疗方法，用于治疗ADPKD儿童和年轻人中研究不足的动脉功能障碍，可能还有肾囊性疾病。

 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.