1/2 + PROmote weight loss in obese PAD patients to preVEnt mobility loss: the PROVE Trial

Proven试验的项目摘要 超过65%的下肢周围动脉疾病(PAD)患者超重或肥胖。 超重或肥胖的PAD患者功能损害更大，功能下降更快 比正常体重的PAD患者要高。步行锻炼是改善功能表现的一线治疗方法 在PAD中。然而，我们的观察纵向数据显示，超重和肥胖的PAD参与者 与步行锻炼相比，减肥和步行锻炼相结合的功能下降较小，但 没有减掉体重。因此，我们假设，在超重或肥胖的PAD患者中， 减肥干预结合运动(WL+EX)对步行能力的改善作用明显优于单独运动。 然而，患有PAD的超重/肥胖者故意减肥的效果尚不清楚，可能 如果减肥加剧了与垫子相关的石棺减少，那就没有好处了。实现可持续的行为改变 WL在患有慢性病的老年肥胖者中具有挑战性。因此，在患有PAD和BMI的人中， Kg/m2，我们将测试WL+EX在功能表现上比WL+EX有更大的改善这一假设 前男友独自一人。我们的创新减肥干预使用了一种群体中介的认知行为框架， 互联移动技术、教练远程监控和卡路里限制仪表板 OMNI心脏节食。在一项为期七周的初步研究中，我们的干预措施平均减轻了5.6磅的体重， 体重指数为28 kg/m2的8名PAD参与者将6分钟步行时间提高了64.1米。 临床前证据表明，肥胖与肢体血流灌注受损有关。人类证据 表明肥胖与骨骼肌线粒体生物合成和活性降低有关。这些 肥胖相关的变化加剧了PAD的病理生理。因此，我们假设体重减轻 将改善行走能力，部分是通过改善小腿的血流，增加小腿线粒体的活动。 我们将212名患有PAD和BMI&28 kg/m2的参与者随机分为两组，为期12个月： WL+EX与单独的EX。参与者将从西北大学、杜兰大学和 明尼苏达州大学。我们的主要结果是在12个月的随访中6分钟步行距离的变化。 次要结果是6个月后6分钟步行距离的变化和锻炼的变化 依从性、体力活动、患者报告的步行能力(以步行障碍衡量 问卷)和生活质量(以SF12身体成分评分衡量)。 第三结果包括核磁共振测量的小腿血流，核磁共振测量的小腿肌肉数量和脂肪。 丰富度和饮食质量。我们将对50名参与者进行小腿肌肉活组织检查，以测量线粒体 生物发生和活动、毛细血管密度、炎症和衰老细胞的丰度。如果我们的假设是 正确，Proven试验将通过预防功能衰退和移动性对公共健康产生重大影响 大量且不断增加的PAD患者超重或肥胖的人数减少。

PROJECT SUMMARY for the PROVE Trial More than 65% of people with lower extremity peripheral artery disease (PAD) are overweight or obese. People with PAD who are overweight or obese have greater functional impairment and faster functional decline than normal weight people with PAD. Walking exercise is first line therapy to improve functional performance in PAD. However, our observational longitudinal data show that overweight and obese PAD participants who combined weight loss with walking exercise had less functional decline than those who walked for exercise but did not lose weight. Therefore, we hypothesize that among people with PAD who are overweight or obese, a weight loss intervention combined with exercise (WL+EX) will improve walking ability more than EX alone. However, effects of intentional weight loss in overweight/obese people with PAD are unknown and may not be beneficial if weight loss exacerbates PAD-related sarcopenia. Behavior change that achieves sustained WL is challenging in older obese people with chronic disease. Therefore, among people with PAD and BMI>28 kg/m2, we will test the hypothesis that WL+EX achieves greater improvement in functional performance than EX alone. Our innovative weight loss intervention uses a group mediated cognitive behavioral framework, connective mobile technology, remote monitoring by a coach, and a calorie restricted DASH-derived OMNIHeart diet. In a seven week pilot study, our intervention achieved mean weight loss of 5.6 pounds and improved the 6-minute walk by 64.1 meters in eight PAD participants with BMI> 28 kg/m2. Preclinical evidence shows that obesity is associated with impaired limb perfusion. Human evidence shows that obesity is associated with reduced skeletal muscle mitochondrial biogenesis and activity. These obesity related changes exacerbate the pathophysiology of PAD. Therefore, we hypothesize that weight loss will improve walking ability in part by improving calf perfusion, and increasing calf mitochondrial activity. We will randomize 212 participants with PAD and BMI > 28 kg/m2 to one of two groups for 12 months: WL+ EX vs. EX alone. Participants will be randomized from Northwestern University, Tulane University, and the U. of Minnesota. Our primary outcome is change in six-minute walk distance at 12-month follow-up. Secondary outcomes are change in 6-minute walk distance at 6-month follow-up and change in exercise adherence, physical activity, patient-reported walking ability (measured by the Walking Impairment Questionnaire), and quality of life (measured by the SF12 Physical Component Score) at 12-month follow-up. Tertiary outcomes include MRI measured calf perfusion, MRI-measured calf muscle quantity and fat abundance, and diet quality. We will perform calf muscle biopsies in 50 participants to measure mitochondrial biogenesis and activity, capillary density, inflammation, and senescent cell abundance. If our hypotheses are correct, the PROVE Trial will have a major public health impact by preventing functional decline and mobility loss in the large and growing number of people with PAD who are overweight or obese.