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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 随着慢性肾脏病（CKD）向终末期肾脏病（ESRD）的发展和进展，营养不良成为日益严重的问题。 这被认为是由两种机制引起的：继发于尿毒症的食欲下降和分解代谢炎症环境的发展。 患者经历肌肉质量和功能活动减少，与发病率和死亡率增加相关。 许多改善营养不良状态的疗法都收效甚微。 生长激素（GH）和胰岛素样生长激素（IGF-I）改善肌肉质量、生活质量、营养参数、免疫和身体功能，但必须胃肠外给予，并且受到费用和患者依从性的限制。 最近，内源性GH受体促分泌素（GHRS）ghrelin已被证明可以提高内源性GH并改善食物摄入，但必须通过胃肠外给药，并且不可用。 实验药物MK-0677是一种合成的GHRS，口服的ghrelin模拟物，最近已被证明可以增加老年人的IGF-I和肌肉质量。 其对CKD和ESRD的影响尚不清楚。 我们将研究MK-0677对肾病患者的影响。 具体来说，我们希望表明该药物增加肾脏患者的IGF-1，并具有与外源性GH和IGF-1相似的作用。 受试者为ESRD血液透析患者。本方案是一项药物启动、随机、双盲、交叉、安慰剂对照的初步研究。该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、生长激素释放肽、TNF-α、CRP、IL-1、IL-6、IL-10和脂联素的水平。 我们希望在这项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.