Ghrelin and Strength Training in Frail Elderly

描述(由申请人提供)：虚弱是一种老年综合症，对压力因素的脆弱性增加，导致身体恶化，并给卫生保健系统带来重大的经济负担。虚弱的主要组成部分包括肌肉质量和质量的丧失(石棺减少)，以及由于能量摄入和消耗不匹配而导致的无意体重减轻。目前还没有批准的治疗虚弱的方法。随着越来越多的人活到80岁的S和90岁的S，开发能够改善虚弱个体的健康和生活质量的疗法是当务之急。Ghrelin是一种由胃产生的激素，它刺激大脑中的食欲中枢。它已经在300多名人类身上进行了研究，包括那些患有导致恶病质的特定疾病(如肾功能衰竭、癌症)的人，但没有在虚弱的人身上进行研究。这一探索性的、发展中的R21的总体目的是收集必要的数据和经验，为Ghrelin和耐药性训练的临床试验做准备。我们假设，Ghrelin和基于家庭的阻力训练的联合干预将改善虚弱老年人的力量和下肢功能。在拟议的R21中，我们试图研究这种干预在70岁及以上虚弱男性和女性中的安全性和有效性的可行性并获得数据。在目标1中，我们将确定虚弱个体的最佳Ghrelin皮下剂量。在目标2中，我们将在一项为期7天的每日重复剂量研究中检查该剂量。在目标3中，我们将对虚弱的个体进行为期12周的家庭力量训练干预的试点研究，包括使用和不使用Ghrelin的干预。这项研究将首次单独并结合阻力训练检查虚弱个体皮下注射生长激素的情况。我们的研究将为完善未来的临床试验提供必要的数据，以测试Ghrelin和抵抗力训练作为改善脆弱个体健康和功能的联合干预措施。

DESCRIPTION (provided by applicant): Frailty is geriatric syndrome of increased vulnerability to stressors that leads to physical deterioration and a significant economic burden to the health care system. Key components of frailty include loss of muscle mass and quality (sarcopenia) and unintentional weight loss resulting from a mismatch between energy intake and expenditure. There are currently no approved therapies for frailty. As increasing numbers of individuals survive to their 80's and 90's, it is imperative to develop therapies that improve the health and quality of life of frail individuals. Ghrelin is a hormone produced by the stomach that stimulates appetite centers in the brain. It has been studied in over 300 humans, including those with specific diseases that cause cachexia (e.g. renal failure, cancer), but not in frail individuals. The overall purpose of this exploratory, developmental R21 is to gather the essential data and experience in preparation for a clinical trial of ghrelin and resistance training. We hypothesize that a joint intervention of ghrelin plus home-based resistance training will improve strength and lower extremity function in frail older individuals. In the proposed R21, we seek to examine the feasibility and obtain data on the safety and efficacy of this intervention in frail men and women aged 70 and older. In Aim 1, we will determine the optimal subcutaneous ghrelin dose in frail individuals. In Aim 2, we will examine this dose in a 7-day repeated daily dose study. In Aim 3, we will execute a 12 week pilot study of a home-based strength training intervention with and without ghrelin administration in frail individuals. This study will be the first to examine subcutaneous ghrelin administration in frail individuals, by itself and combined with resistance training. Our study will provide essential data to refine a future clinical trial to test ghrelin and resistance training as a joint intervention to improve the health and function of individuals with frailty.