Ghrelin and Strength Training in Frail Elderly

描述（由申请人提供）：虚弱是一种老年综合征，易受压力的影响，导致身体恶化，给医疗保健系统带来重大经济负担。虚弱的关键组成部分包括肌肉质量和质量的损失（肌肉减少症）以及由于能量摄入和消耗之间的不匹配而导致的无意体重减轻。目前没有批准的虚弱疗法。随着越来越多的人活到80多岁和90多岁，开发改善体弱者健康和生活质量的疗法势在必行。Ghrelin是一种由胃产生的激素，它刺激大脑中的食欲中心。它已经在超过300人中进行了研究，包括那些患有引起恶病质的特定疾病（例如肾衰竭，癌症）的人，但不是虚弱的人。这个探索性的，发展性的R21的总体目的是收集必要的数据和经验，为生长激素释放肽和阻力训练的临床试验做准备。我们假设，联合干预生长激素释放肽加家庭阻力训练将改善力量和下肢功能，在体弱的老年人。在拟议的R21中，我们试图检查这种干预措施在70岁及以上体弱男性和女性中的安全性和有效性的可行性并获得相关数据。在目标1中，我们将确定虚弱个体的最佳皮下ghrelin剂量。在目标2中，我们将在7天重复每日剂量研究中检查该剂量。在目标3中，我们将在虚弱的个体中进行为期12周的基于家庭的力量训练干预的试点研究，其中有和没有ghrelin给药。这项研究将是第一个检查皮下生长激素释放肽管理在虚弱的个人，本身和阻力训练相结合。我们的研究将提供必要的数据，以完善未来的临床试验，以测试ghrelin和阻力训练作为改善虚弱个体健康和功能的联合干预措施。 公共卫生相关性：目前还没有批准的治疗老年人虚弱的疗法。我们的研究将检查激素生长激素的使用，它刺激食欲，结合阻力训练，以提高虚弱的老年人的力量和功能。

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. PUBLIC HEALTH RELEVANCE: There are currently no approved therapies to treat frailty in the elderly. Our study will examine the use of the hormone ghrelin, which stimulates appetite, in conjunction with resistance training to improve strength and function in frail older individuals.