Planning Grant for an Intensive Weight Loss Clinical Trial for Overweight and Obese Patients Post Total Knee Replacement

该提案是对NIH计划公告PAR 16 -446“NIAMS临床试验”的回应 规划补助金（R34）。众所周知，肥胖与许多医学问题有关， 高血压、糖尿病和心脏病以及早期膝关节骨关节炎。大型临床试验，如 展望未来（糖尿病健康行动）已经表明，多组分减肥干预措施 结合饮食、体育活动和行为改变是实现长期健康的最有效方法。 体重减轻（1，2）。因此，临床实践指南建议对肥胖症患者进行干预， 许多健康状况。全膝关节置换术（TKR）手术的流行率 在过去的几十年里，在美国，超重和肥胖患者呈指数级增长， 在其一生中需要TKR的风险特别高（3-5）。更令人震惊的事实是， 超重或肥胖患者接受了TKR，他们不太可能减轻体重，而更可能增加体重 术后体重增加。不幸的是，随着BMI的增加， TKR，除了需要TKR外，未来需要对当前TKR进行翻修的可能性更大， 对侧肢（6）。这一不幸的范例为超重和肥胖者提供了一个不断积累的差距 TKR患者人群。尽管这种差距不断扩大，但目前的文献中没有研究 在接受TKR的超重和肥胖个体中长期减肥的有效性持续存在。 因此，目前尚不清楚多组分减肥干预是否对患者有益。 接受过TKR的超重和肥胖人群亚组。为了解决这一问题，我们 提出一项临床试验计划拨款，以转化成功的Look AHEAD强化生活方式 在TKR术后超重和肥胖患者中使用的干预（ILI），并计划未来的研究来测试 Look AHEAD ILI是否会导致该高危人群的体重显著减轻。我们进一步 我建议测试这些体重减轻的变化是否会转化为超重患者的功能改善。 与接受标准护理支持和教育的患者相比， 一个人规划补助金将分两个阶段进行：形成性评估阶段（第1阶段）和U 01， 临床试验开发阶段（第2阶段）。在第1阶段，我们将成功的Look AHEAD ILI修改为 适用于超重和肥胖TKR患者人群的特定需求。在第二阶段，我们将 概述ILI的具体修改，开发适当的统计分析，并最终确定我们的方案 利用通过焦点小组和关键线人访谈收集的信息，为U 01的发展提供信息 临床试验申请。考虑到需要TKR的超重和肥胖患者的流行比例 手术，我们相信这项研究的健康和经济影响将是不可估量的。

This proposal is in response to the NIH Program Announcement PAR16-446 titled “NIAMS Clinical Trial Planning Grant (R34).” It is well known that obesity has been linked to many medical issues such as hypertension, diabetes and heart disease, as well as to early knee osteoarthritis. Large clinical trials, such as Look AHEAD (Action for Health in Diabetes), have shown that multicomponent weight loss interventions combining diet, physical activity, and behavioral modification are the most effective in achieving long-term weight loss (1, 2). As a result, clinical practice guidelines recommend the delivery of obesity interventions for numerous health conditions. The prevalence of the total knee replacement (TKR) surgical procedure has increased exponentially in the United States over the last few decades and overweight and obese patients are at particularly high risk of needing a TKR during their lifetime (3-5). A more alarming fact is that once an overweight or obese patient has undergone TKR, they are less likely to lose weight and are more likely to gain additional weight post-surgery. Unfortunately, with increases in BMI comes decreases in functionality of the TKR and greater likelihood of need for future revision of the current TKR in addition to need for TKR of the opposite limb (6). This unfortunate paradigm presents an accumulating disparity for the overweight and obese TKR patient population. Despite this ever-growing disparity, a void in the current literature examining the efficacy of long term weight loss in overweight and obese individuals who have undergone TKR persists. Therefore, it remains unknown if a multicomponent weight loss intervention would be beneficial to the subset of the overweight and obese population who have undergone TKR. To address this disparity, we propose a clinical trial planning grant to translate the successful Look AHEAD intensive lifestyle intervention (ILI) for use in overweight and obese post TKR patients, and to plan a future study to test whether the Look AHEAD ILI will result in significant weight loss in this at-risk population. We further propose to test whether these weight loss changes translate into functional improvements in the overweight and obese post TKR patient population compared to those receiving standard of care support and education alone. The planning grant will be conducted in 2 stages: a formative assessment stage (stage 1) and a, U01, clinical trial development stage (stage 2). During stage 1 we will modify the successful Look AHEAD ILI to be applied to the specific needs of the overweight and obese TKR patient population. During stage 2 we will outline the specific ILI modifications, develop the appropriate statistical analyses, and finalize our protocols utilizing information gathered via focus groups and key informant interviews to inform development the U01 clinical trial application. Given the epidemic proportion of overweight and obese patients requiring TKR surgery, we believe the health and economic impact of this study will be immeasurable.