Role of IL-6 in Regulating Energy Stores During Recovery From an Acute Exercise Bout
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in muscle expression of fatty acid transporter 4 (FATP4)
研究概览
简要总结
The aim of the study is to investigate the role of exercise-induced IL-6 in regulating energy stores and energy metabolism during recovery after an acute exercise bout. To achieve this, 30 men will be randomized to infusion placebo or tocilizumab (IL-6 receptor antibody) combined with a 2-hour exercise bout. Stable isotope tracers will be infused to determine substrate kinetics. Indirect calorimetry will be applied to determine substrate oxidation, and muscle biopsies will be taken to determine substrate uptake and storage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
Participants and investigators will be blinded to the infusion of saline or tocilizumab
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Physically active (defined as meeting the ACSM's guidelines of 2.5h per week of moderate to vigorous physical activity per week), young, healthy males will be included. Participants may be included in the study if they meet all the following criteria:
- •Age ≥ 18 years and ≤ 40 years
- •BMI < 18 and > 25 kg/m2
- •Healthy (based on screening)
- •Stable body weight for 6 months
- •≥ 2.5h/week moderate to vigorous physical activity
排除标准
- •• Cardiovascular disease
- •Rheumatologic disease
- •Metabolic disease
- •Elite sports or high aerobic training status (VO2max > 60 mL O2/min/kg)
- •Frequent/chronic use of medications affecting physical performance or inflammation (NSAIDS, DMARDS, corticosteroids)
- •Aspirin use >100 mg/d
- •Thyroid disease
- •Current infection
- •Aspartate amino transferase (AST) or alanine amino transferase (ALT) >2x upper normal range
- •History of carcinoma
- •History of tuberculosis
- •Ketogenic diet
- •Anemia (hematocrit <33%)
- •Neutrophil count <0,5x 109/l
- •Thrombocytes <50x 109/l or bleeding disorders
研究组 & 干预措施
Tocilizumab
Participants will receive one 30 min intravenous infusion of tocilizumab/Actemra® (Roche). The dose will be 8 mg/kg bodyweight or a maximum of 800mg. Tocilizumab is dissolved in 100 mL 0.9% saline.
干预措施: Tocilizumab/Actemra® (Roche) (Drug)
Saline
As placebo, participants will receive one 30 min intravenous infusion of 100 mL 0.9% saline.
干预措施: Saline 9% (Drug)
结局指标
主要结局
Change in muscle expression of fatty acid transporter 4 (FATP4)
时间窗: Measured at 0, 120 and 360 min
Comparing muscle expression of FATP4 before and immediately after exercise and 4 hours after recovery in the two groups
Change in muscle glycogen content (mmol/kg/h)
时间窗: Measured at 0, 120, 180 and 360 minutes
Comparing change in muscle glycogen in the two groups from before exercise to immediately after exercise, and after 1 hour and 4 hours of recovery
Change in muscle expression of muscle fatty acid binding protein (FABPm)
时间窗: Measured at 0, 120 and 360 min
Comparing muscle expression of FABPm before and immediately after exercise and 4 hours after recovery in the two groups
Change in muscle expression of glycerol transporters
时间窗: Measured at 0, 120 and 360 min
Comparing muscle expression of glycerol transporters before and immediately after exercise and 4 hours after recovery in the two groups
Change in muscle triglycerides content
时间窗: Measured at 0, 120, 180 and 360 minutes
Comparing change in muscle triglycerides in the two groups from before exercise to immediately after exercise, and after 1 hour and 4 hours of recovery
Change in muscle expression of glucose transporter type 4 (GLUT4)
时间窗: Measured at 0, 120 and 360 min
Comparing muscle expression of GLUT4 before and immediately after exercise and 4 hours after recovery in the two groups
Change in muscle expression of fatty acid translocase (FAT/CD36)
时间窗: Measured at 0, 120 and 360 min
Comparing muscle expression of FAT/CD36 before and immediately after exercise and 4 hours after recovery in the two groups
次要结局
- Change in glucose enrichment in intramuscular glycogen(Measured at 0, 120, 180 and 360 minutes)
- Change in palmitate concentration(Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in palmitate enrichment in intramuscular triglycerides(Measured at 0, 120, 180 and 360 minutes)
- Change in intramuscular triglycerides fractional synthesis rate(Measured at 0, 120, 180 and 360 minutes)
- Change in plasma IL-8 concentration(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in plasma IL-4 concentration(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in glycogen fractional synthesis rate(Measured at 0, 120, 180 and 360 minutes)
- Change in glucose rate of appearance(Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in gylcerol rate of appearance(Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in palmitate rate of appearance(Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in plasma IL-6 concentration(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in plasma IL-1beta concentration(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in plasma IL-1Ra concentration(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in insulin(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in glucose rate of disappearance(Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in intramuscular glucose concentration(Measured at 0, 120, 180 and 360 minutes)
- Change in palmitate rate of disappearance(Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in plasma IL-10 concentration(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in glucose concentration(Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in intramuscular palmitate content(Measured at 0, 120, 180 and 360 minutes)
- Change in gylcerol rate of disappearance(Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in gylcerol concentration(Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in palmitate oxidation(Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in haemoglobin(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in haematocrit(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in differential blood count(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in plasma TNF-alpha concentration(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in c-peptide(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in triglycerides(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in plasma sIL-6R concentration(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in noradrenaline(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in total glucagon-like peptide-1 (GLP-1)(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in glucagon(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in growth hormone (GH)(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in adrenaline(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in cortisol(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in active GLP-1(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in gastric inhibitory peptide (GIP)(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in leptin(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
- Change in peptide YY (PYY)(Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes)
研究者
Helga Ellingsgaard
PhD, Group leader, Centre for Physical Activity Research
Rigshospitalet, Denmark