Sit Less, Interact and Move More (SLIMM) 2 Study

久坐行为是指在坐着或躺着的姿势下几乎不能增加能量的活动 支出高于静息代谢率，是肥胖、糖尿病和心血管疾病的危险因素 和死亡率。然而，中等强度/剧烈的体育活动不太可能是一种有效的 替代CKD患者的久坐活动，因为大多数健康的美国人甚至不会 实现这些活动的当前目标。因此，在NIDDK资助的试点和可行性RCT中 (R21DK106574，PI：Beddhu)，我们测试了一种‘少坐，多互动，多移动(SLIMM)’的可行性 对106名慢性肾脏病患者进行干预，将久坐活动改为随意的踏步活动。在 Slimm组久坐时间最大减幅(-43.0，95%CI-69.0~-17.0分钟/天)和 增加步进持续时间(15.5，95%CI 6.9至24.1min/天)和步数(1265，95%CI 518至2012年)在第20周可见，但在第24周减弱。在事后描述性分析中，更高 通过6分钟步行距离和较低基线体脂百分比来证明基线身体功能 在SLIMM组中，生物阻抗似乎与SLIMM干预目标的实现有关。 基于我们在SLIMM试点研究中的观察，我们提出了久坐之间复杂的相互作用 行为、身体功能受损和肥胖导致长期久坐不动的恶性循环 CKD中的行为。因此，对久坐行为的成功干预将需要纳入共同的 针对肥胖和身体功能受损的干预措施。具体地说，我们建议增加指导性 耐力训练以增加身体功能和半谷氨酸，一种胰高血糖素样肽-1(GLP-1)受体 一种激动剂，已被证明可以减少肥胖和炎症，并提高与健康相关的生活质量。 在此，我们寻求在前三个月单独实施SLIMM干预，然后是9个月 SLIMM+标准治疗RT+安慰剂、SLIMM+引导RT+安慰剂和 Slimm+导向RT+口服赛马路德治疗156例超重或肥胖的中晚期CKD患者。 指定的主要终点减少了久坐时间，关键的次要终点是6- 步行一分钟即可到达。我们还将探索干预措施对体脂百分比的影响，患者报告 结果，下肢功能电池和炎症标志物。 这两家机构都有大量潜在的参与者。这项研究有足够的动力来 检测久坐时间和其他终点的显著减少。这个由多个学科组成的团队 经验丰富的调查人员有成功开展随机对照试验的良好记录。这项建议是 可行、创新，并可能产生信息丰富的结果。如果干预措施减少 CKD的久坐行为，这项试验将为更大规模的久坐行为干预RCT铺平道路 硬终端。

Sedentary behavior is engaging in activities in the seated or lying position that barely raise the energy expenditure above the resting metabolic rate and is a risk factor for obesity, diabetes, cardiovascular disease and mortality. However, it is unlikely that moderate/ vigorous intensity physical activities could be an effective replacement for sedentary activities for persons with CKD as most otherwise healthy Americans do not even reach the current goals for these activities. Therefore, in a NIDDK funded pilot and feasibility RCT (R21DK106574, PI: Beddhu), we tested, the feasibility of a `Sit Less, Interact, Move More (SLIMM)' intervention to replace sedentary activities with casual stepping activities in 106 participants with CKD. In the SLIMM group, the maximum decrease in sedentary duration (-43.0, 95% CI --69.0 to -17.0 min/day) and increase in stepping duration (15.5, 95% CI 6.9 to 24.1 min/day) and the number of steps/day (1265, 95% CI 518 to 2012) were seen at week 20 but attenuated at week 24. In post-hoc, descriptive analyses, higher baseline physical function as evidenced by 6-min walk distance and lower baseline body fat% measured by bio-impedance appeared to be associated with achieving SLIMM intervention goals in the SLIMM group. Based on our observations in the SLIMM pilot study, we propose a complex interplay between sedentary behavior, impaired physical function and obesity that leads to a vicious cycle that perpetuates sedentary behavior in CKD. Therefore, a successful intervention for sedentary behavior will need to incorporate co- interventions targeting obesity and impaired physical function. Specifically, we propose the addition of guided resistance training to increase physical function and semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist that has been shown to decrease adiposity and inflammation and improve health related quality of life. Herein we seek to implement SLIMM intervention alone for the first three months followed by a 9 month RCT of three equal groups of SLIMM + standard of care RT + placebo, SLIMM + guided RT + placebo and SLIMM + guided RT + oral semaglutide in 156 overweight or obese patients with moderate to advanced CKD. The designated primary endpoint is decrease in sedentary duration and the key secondary endpoint is six- minute walk distance. We will also explore the effects of the interventions on body-fat%, patient reported outcomes, lower extremity performance battery and markers of inflammation. There is a large pool of potential participants in the two institutions. The study is adequately powered to detect meaningful decrease in sedentary duration and other endpoints. This multi-disciplinary team of experienced investigators have a proven track record of successfully conducting RCTs. This proposal is feasible, innovative, and likely to yield results that will be informative. If the interventions decrease sedentary behavior in CKD, this trial will pave the way for larger RCTs of sedentary behavior interventions on hard endpoints.