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

生长激素分泌剂 MK-677 对 CKD 中 IGF-1 水平的治疗效果

• 批准号: 7951486
• 负责人: Warren Kline BOLTON
• 金额: $ 4.58万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951486
• 关键词: Chronic Kidney Failure; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Desire for food; Development; Double-Blind Method; Eating; Elderly; End stage renal failure; Funding; Goals; Grant; Hemodialysis; Immune; Inflammatory; Institution; Insulin; Insulin-Like Growth Factor I; Interleukin-1; Interleukin-10; Interleukin-6; Kidney; Leptin; MK-677; Malnutrition; Morbidity - disease rate; Nutritional; Patients; Pharmaceutical Preparations; Phase; Physical Function; Pilot Projects; Placebo Control; Protocols documentation; Quality of life; Randomized; Research; Research Personnel; Resources; Secondary to; Somatotropin; Source; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Uremia; adiponectin; compliance behavior; cytokine; economic impact; esterase; experience; ghrelin; growth hormone secretagogue receptor; human GHR protein; human TNF protein; improved; mimetics; mortality; muscle form; nutrition; primary outcome; secondary outcome; success

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 随着慢性肾脏病（CKD）向终末期肾病（ESRD）的发展和进展，营养不良成为一个日益严重的问题。 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。 患者的肌肉质量和功能活动减少，从而导致发病率和死亡率增加。 许多改善营养不良状态的疗法已被使用，但收效甚微。 生长激素 (GH) 和类胰岛素生长激素 (IGF-I) 可以改善肌肉质量、生活质量、营养参数、免疫和身体功能，但必须在肠外给药，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) 生长素释放肽已被证明可以提高内源性 GH 并改善食物摄入量，但必须通过肠胃外给药，目前还没有。 实验药物 MK-0677 是一种合成的 GHRS（生长激素释放肽模拟物），口服给药，最近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 对肾脏患者的影响。 具体来说，我们希望表明该药物可以增加肾脏患者的IGF-1，并且与外源性GH和IGF-1具有相似的效果。 受试者将是 ESRD 血液透析患者。该方案是一项由研究者发起、随机、双盲交叉、安慰剂对照的试点研究。该研究的主要结果是受试者的 IGF-1 水平。 次要结果是细胞因子、酯酶、瘦素、胰岛素、生长素释放肽、TNF-α、CRP、IL-1、IL-6、IL-10 和脂联素的水平。 我们希望在这个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病患者，并具有更广泛的目标，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。