GROWTH HORMONE SECRETAGOGUE MK-677 THERAPY EFFECT ON IGF-1 LEVELS IN CKD & ESRD

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 随着慢性肾脏病(CKD)向终末期肾病(ESRD)的发展，营养不良成为一个日益严重的问题。这被认为是通过两种机制发生的：继发于尿毒症的食欲下降和分解代谢炎症环境的发展。患者的肌肉质量和功能活动减少，发病率和死亡率增加。许多改善营养不良状态的治疗方法都没有什么效果。生长激素(GH)和胰岛素样生长激素(IGF-I)可改善肌肉质量、生活质量、营养参数、免疫和身体功能，但必须由父母服用，并受到费用和患者依从性的限制。最近，内源性生长激素受体促分泌剂(GHRS)Ghrelin被证明可以提高内源性GH和改善食物摄入量，但必须由父母给药，目前还没有。实验药物MK-0677是一种合成的GHRS，口服的Ghrelin模拟物，最近被证明可以增加老年人的IGF-I和肌肉质量。其在慢性肾脏病和终末期肾病中的作用尚不清楚。我们将研究MK-0677对肾病患者的影响。具体地说，我们希望证明该药物增加肾脏患者的IGF-1，并具有类似于外源性GH和IGF-1的作用。研究对象将是终末期肾病血液透析患者。该方案是一项由研究人员发起的、随机、双盲交叉、安慰剂对照的先导性研究。这项研究的主要结果是受试者的IGF-1水平。次要结果将是细胞因子、酯酶、瘦素、胰岛素、Ghrelin、肿瘤坏死因子-α、CRPS、IL-1、IL-6、IL-10和脂联素的水平。 我们希望在这一短期试验之后进行更大规模的2b期研究。2b期研究将包括慢性肾脏疾病患者，并有更广泛的目标，包括：MK-0677对肌肉质量、营养、食欲、身体功能、生活质量和经济影响的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. With development and progression of chronic kidney disease (CKD) to end stage renal disease (ESRD), malnutrition becomes an increasingly severe problem. This is thought to occur from two mechanisms: decreased appetite secondary to uremia and development of a catabolic inflammatory milieu. Patients experience decreased muscle mass and functional activity associated with increased morbidity and mortality. Many therapies to improve poor nutritional state have been used with little success. Growth hormone (GH) and insulin like growth hormone (IGF-I) improve muscle mass, quality of life, nutritional parameters, immune and physical functions but must be given parentally and are limited by expense and patient compliance. Recently, the endogenous GH receptor secretagogue (GHRS) ghrelin has been shown to raise endogenous GH and improve food intake but must be given parentally and is not available. The experimental drug, MK-0677, a synthetic GHRS, ghrelin mimetic which is given orally, has recently been shown to increase IGF-I and muscle mass in the elderly. Its effects in CKD and ESRD are unknown. We will study the effects of MK-0677 on renal patients. Specifically, we hope to show that the drug increases IGF-1 in renal patients, and has similar effects to exogenous GH and IGF-1. Subjects will be ESRD hemodialysis patients. This protocol is an investigator-initiated, randomized, double-blind crossover, placebo-controlled pilot study. The study's primary outcome is IGF-1 levels for subjects. Secondary outcomes will be levels of cytokines, esterase, leptin, insulin, ghrelin, TNF- alpha, CRPs, IL-1, IL-6 IL-10, and adiponectin. We hope to follow this short trial with a larger phase 2b study. The phase 2b study will include chronic kidney disease patients and have broader goals including: MK-0677 effects on muscle mass, nutrition, appetite, physical function, quality of life and economic impact.