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

久坐行为是指在坐着或躺着的位置上从事几乎不能提高能量的活动 消耗高于静息代谢率，是肥胖、糖尿病、心血管疾病的危险因素 and mortality.然而，中等/剧烈强度的体力活动不太可能是有效的 代替CKD患者的久坐活动，因为大多数其他健康的美国人甚至 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， （R21 DK 106574，PI：Beddhu），我们测试了“少坐，互动，多动（SLIMM）”的可行性。 在106名CKD参与者中进行干预，用随意的步行活动代替久坐活动。在 SLIMM组，久坐持续时间的最大减少（-43.0，95%CI--69.0至-17.0 min/d）， 步行持续时间（15.5，95% CI 6.9 - 24.1分钟/天）和步数/天（1265，95% CI）增加 518至2012），但在第24周减弱。在事后描述性分析中， 基线身体功能（通过6分钟步行距离证明）和较低的基线体脂%（通过测量） 在SLIMM组中，生物阻抗似乎与实现SLIMM干预目标相关。 根据我们在SLIMM试点研究中的观察，我们提出了久坐与肥胖之间的复杂相互作用。 行为，身体功能受损和肥胖，导致一个恶性循环，使久坐不动 CKD中的行为。因此，一个成功的干预久坐行为将需要纳入共同的， 针对肥胖和身体功能受损的干预措施。具体来说，我们建议增加指导性的 通过阻力训练增加身体功能和Semaglutide（胰高血糖素样肽-1（GLP-1）受体） 激动剂，已被证明可以减少肥胖和炎症，并改善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 +指导RT +安慰剂三个相等组的RCT SLIMM +指导RT +口服semaglutide治疗156例超重或肥胖中晚期CKD患者。 指定的主要终点是久坐时间的减少，关键的次要终点是六个- 分钟步行距离。我们还将探讨干预措施对体脂%的影响， 结果、下肢功能测试和炎症标志物。 这两个机构的潜在参与者很多。本研究有足够的把握度， 检测久坐持续时间和其他终点的有意义的减少。这个多学科的团队 经验丰富的研究者具有成功开展RCT的良好记录。这项建议是 可行的，创新的，并可能产生的结果，将是翔实的。如果干预减少， 这项试验将为更大规模的久坐行为干预措施的RCT铺平道路， 硬端点

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.