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，对压力源的脆弱性增加，导致身体恶化和医疗保健系统的重大经济负担。虚弱的关键因素包括肌肉量和质量的减少（肌肉减少症）和能量摄入和消耗之间不匹配导致的意外体重减轻。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岁和90岁，开发改善体弱个体健康和生活质量的治疗方法势在必行。胃饥饿素是一种由胃产生的激素，可以刺激大脑的食欲中心。它已经在300多人身上进行了研究，包括那些患有导致恶病质的特定疾病的人（如肾衰竭、癌症），但没有在虚弱的人身上进行研究。这个探索性、发展性R21的总体目的是收集必要的数据和经验，为胃饥饿素和抗阻训练的临床试验做准备。我们假设胃饥饿素联合干预加上家庭阻力训练将改善体弱老年人的力量和下肢功能。在拟议的R21中，我们试图检查这种干预在70岁及以上的体弱男性和女性中的可行性并获得安全性和有效性的数据。在目的1中，我们将确定体弱个体的最佳皮下胃饥饿素剂量。在Aim 2中，我们将在7天的重复日剂量研究中检查该剂量。在Aim 3中，我们将对体弱个体进行为期12周的以家庭为基础的力量训练干预，包括和不包括胃促生长素。这项研究将首次对体弱者单独或联合抗阻训练进行胃饥饿素皮下注射的研究。我们的研究将为完善未来的临床试验提供必要的数据，以测试胃饥饿素和抗阻训练作为联合干预措施，以改善虚弱个体的健康和功能。

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.