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

1/2 促进肥胖 PAD 患者减肥以防止活动能力丧失：PROVE 试验

• 批准号: 10026434
• 负责人: Mary McGrae McDermott
• 金额: $ 64.26万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-10 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10026434
• 关键词: Adherence; Animals; Behavioral; Biogenesis; Biopsy; Blood capillaries; Body Weight decreased; Caloric Restriction; Cells; Chronic Disease; Cognitive; Cognitive Therapy; Data; Diet; Exercise; Exertion; Fatty acid glycerol esters; Functional disorder; Funding; Horns; Human; Impairment; Inflammation; Interleukin-1 beta; Interleukin-6; Intervention; Isolated limb perfusion; Longitudinal observational study; Lower Extremity; Magnetic Resonance Imaging; Measures; Mediating; Minnesota; Mitochondria; Monitor; Muscle; Muscle Fibers; Muscle Mitochondria; National Heart, Lung, and Blood Institute; Obesity; Outcome; Overweight; Participant; Patients; Performance; Perfusion; Peripheral arterial disease; Physical activity; Pilot Projects; Public Health; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Reporting; Skeletal Muscle; TNF gene; Testing; Universities; Walking; Weight; behavior change; density; enzyme activity; exercise adherence; exercise intervention; follow-up; functional decline; functional disability; improved; innovation; meter; mobile computing; nutrition; pre-clinical; prevent; primary outcome; sarcopenia; secondary outcome; senescence; weight loss intervention

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.

证明审判的项目摘要 超过65％的下肢外围动脉疾病（PAD）超重或肥胖。 超重或肥胖的PAD患者的功能障碍更大，功能下降速度更快 比正常体重的人用垫子。步行运动是提高功能性能的第一线治疗 在垫子中。但是，我们的观察纵向数据表明，超重和肥胖的参与者 与步行运动的人相比，与步行运动相比，体重减轻的功能下降较少，但 没有减肥。因此，我们假设在超重或肥胖的患者中 减肥干预与运动结合（WL+EX）将比单独的EX更具提高步行能力。 但是，超重/肥胖者的故意体重减轻的影响尚不清楚，可能 如果减肥加剧了与垫有关的肌肉减少症，则不是有益的。实现持续的行为改变 WL在老年肥胖患有慢性疾病的人中具有挑战性。因此，在有PAD和BMI> 28的人中 kg/m2，我们将检验以下假设，即WL+EX可以在功能性能方面取得更大的提高 一个人。我们创新的减肥干预使用群体介导的认知行为框架， 结缔组织技术，教练的远程监控以及卡路里受限的仪表板衍生 Omniheart饮食。在一项为期7周的试点研究中，我们的干预措施平均体重减轻了5.6磅， 在BMI> 28 kg/m2的八个PAD参与者中，将64.1米的步行路程提高了64.1米。 临床前证明，肥胖与肢体灌注受损有关。人类证据 表明肥胖与骨骼肌线粒体生物发生和活性减少有关。这些 肥胖相关的变化加剧了PAD的病理生理学。因此，我们假设体重减轻 将通过改善小腿灌注并增加小腿线粒体活性来改善步行能力。 我们将在12个月内将212名参与者随机为两个组之一，并将BMI> 28 kg/m2随机为两个组之一： wl+ ex vs.单独。参与者将从西北大学，杜兰大学和 明尼苏达州。我们的主要结果是在12个月的随访中六分钟步行距离变化。 次要结果是在6个月的随访中步行6分钟的步行路程和锻炼变化 依从性，体育锻炼，患者报告的步行能力（通过步行障碍衡量 问卷）和生活质量（通过SF12物理成分得分衡量），以12个月的随访。 三级结果包括MRI测量的小腿灌注，MRI测量小腿肌肉数量和脂肪 丰度和饮食质量。我们将在50名参与者中进行小腿肌肉活检以测量线粒体 生物发生和活性，毛细血管密度，炎症和衰老细胞丰度。如果我们的假设是 正确，证明试验将通过防止功能下降和流动性产生重大的公共卫生影响 超重或肥胖的大量垫子的损失。