Role of Exercise in the Prevention and Treatment of RAGE-Mediated Inflammation (RECEPTOR) Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Quantify the Percentage Change in Basal Circulating sRAGE After 12-weeks of Supervised Aerobic Exercise Training.
研究概览
简要总结
This study examines the effects of 12-weeks of aerobic exercise training on the mechanisms driving RAGE-mediated inflammation in type 2 diabetic humans.
详细描述
Activation of RAGE (receptor of advanced glycation endproducts (AGEs)), via binding of AGEs and other ligands, modulates the development and progression of diabetic complications through persistent and cyclic activation of nuclear factor-kappa beta. Targeting RAGE directly as a therapeutic strategy has largely been unsuccessful. However, RAGE signaling can be interrupted, in vivo, by ADAM10 (a disintegrin and metalloproteinase 10) directed proteolytic cleavage of the RAGE ectodomain, and thus creating a soluble isoform of RAGE (sRAGE) that is released from the cell and appears into the circulation. Maintaining high levels of circulating sRAGE is advantageous as sRAGE will sequester RAGE ligands and prevent RAGE cell signaling.
Although the exact mechanisms of ADAM10 mediated RAGE release remain undefined, calcium related and other signaling (SIRT1) impact ADAM10. Aerobic exercise presents a unique model for mechanistic study of RAGE release as muscle contraction induces robust calcium signaling, activates SIRT1, and provides stimuli for tissue remodeling and resolution of the metabolic profile that drives inflammation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 40-75 y
- •Type 2 diabetes
- •Overweight or obese (BMI 26-44 kg/m2)
- •Fluency in English (written and verbal)
排除标准
- •Age <40 or >75 y
- •BMI <26 or >44 kg/m2
- •Existing cardiovascular, cerebrovascular, renal, or hematological disease, or cancer
- •Current use of tobacco
- •Pregnant or lactating
- •Medications that may interfere with study outcomes
研究组 & 干预措施
Aerobic Exercise Group
Aerobic Exercise (AE) subjects will come in for supervised, aerobic exercise training sessions 5 days a week for 12 weeks. Training will progress from 55% VO2max for week 1 (40 min session), to 60-65% VO2max for week 2 (50 min session), to ~70% VO2max for all other weeks (50 min session). Subjects will perform a warm-up and cool down (~5 min each) that includes stretching exercises. Subjects will wear heart rate monitors during each training session to provide feedback of target heart rate. Intensity, duration, resting and exercise heart rates, and blood pressures will be recorded for each session. Follow-up VO2max tests will be performed at weeks 4 and 8 to monitor progress and adjust AE training intensity.
干预措施: Aerobic Exercise (Behavioral)
Control Group
During the 12 week control period, subjects are to maintain their normal, daily-living activities. Control group participants will be given the option to enroll in the AE training group after completion of the original Control group trial period.
结局指标
主要结局
Quantify the Percentage Change in Basal Circulating sRAGE After 12-weeks of Supervised Aerobic Exercise Training.
时间窗: Baseline and 12 weeks
Serum will be separated from blood samples collected in vacutainer tubes via centrifugation before and after 12-weeks of aerobic exercise training. sRAGE will be quantified in these serum samples via ELISA (Quantikine, Human RAGE Immunoassay) per manufacture's protocol.
次要结局
- Quantify the Percentage Change in Insulin Sensitivity After 12-weeks of Supervised Aerobic Exercise Training.(Baseline and 12 weeks)
- Quantify the Percentage Change in Aerobic Capacity (VO2max) After 12-weeks of Supervised Aerobic Exercise Training.(Baseline and 12 weeks)
- Quantify the Percentage Change in Basal Muscle RAGE Expression After 12-weeks of Supervised Aerobic Exercise Training.(Baseline and 12 weeks)
研究者
Jacob Haus
Associate Professor
University of Michigan