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

基本信息

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
项目类别：
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

项目摘要

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.

PROVE 试验的项目摘要超过 65% 的下肢外周动脉疾病 (PAD) 患者超重或肥胖。超重或肥胖的 PAD 患者的功能障碍更大，功能衰退更快高于正常体重的 PAD 患者。步行运动是改善功能表现的一线疗法在PAD中。然而，我们的纵向观察数据表明，超重和肥胖的 PAD 参与者与步行锻炼的人相比，减肥与步行锻炼相结合的功能下降较少，但没有减肥。因此，我们假设，在超重或肥胖的 PAD 患者中，减肥干预结合运动（WL+EX）比单独使用EX更能提高步行能力。然而，有意减肥对患有外周动脉疾病（PAD）的超重/肥胖患者的影响尚不清楚，并且可能如果减肥加剧了 PAD 相关的肌肉减少症，则没有益处。实现持续的行为改变对于患有慢性疾病的老年肥胖人群来说，WL 具有挑战性。因此，在 PAD 且 BMI>28 的人群中 kg/m2，我们将检验以下假设：WL+EX 在功能性能方面比 WL+EX 实现了更大的改善 EX一个人。我们创新的减肥干预措施采用群体介导的认知行为框架，连接移动技术、教练远程监控以及源自 DASH 的热量限制 OMNI心脏饮食。在一项为期 7 周的试点研究中，我们的干预措施实现了平均体重减轻 5.6 磅 BMI > 28 kg/m2 的 8 名 PAD 参与者的 6 分钟步行速度提高了 64.1 米。临床前证据表明肥胖与肢体灌注受损有关。人类证据研究表明，肥胖与骨骼肌线粒体生物发生和活性降低有关。这些肥胖相关的变化加剧了 PAD 的病理生理学。因此我们推测减肥将通过改善小腿灌注和增加小腿线粒体活性来部分提高步行能力。我们将 212 名 PAD 且 BMI > 28 kg/m2 的参与者随机分为两组，为期 12 个月： WL+ EX 与单独 EX 的比较。参与者将随机来自西北大学、杜兰大学和明尼苏达大学。我们的主要结果是 12 个月随访时六分钟步行距离的变化。次要结果是 6 个月随访时 6 分钟步行距离的变化以及运动量的变化依从性、体力活动、患者报告的步行能力（通过步行障碍来衡量）调查问卷），以及 12 个月随访时的生活质量（通过 SF12 身体成分评分衡量）。第三个结果包括 MRI 测量的小腿灌注、MRI 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，PROVE 试验将通过防止功能衰退和活动能力产生重大公共卫生影响大量且不断增加的超重或肥胖 PAD 患者数量减少。