Glycogen Depletion
Conditions
Brief summary
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.
Interventions
DRUGTocilizumab/Actemra® (Roche)
The infusion of tocilizumab will antagonize IL-6 signaling for the duration of the study, allowing us to determine the role of IL-6 in regulating energy stores following acute exercise
DRUGSaline 9%
The infusion of saline will serve as placebo for tocilizumab, allowing us to determine the role of IL-6 in regulating energy stores following acute exercise
Sponsors
Helga Ellingsgaard
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants and investigators will be blinded to the infusion of saline or tocilizumab
Intervention model description
Randomized, placebo-controlled, double-blind
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* • 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 * Smoking * Anemia (hematocrit \<33%) * Neutrophil count \<0,5x 109/l * Thrombocytes \<50x 109/l or bleeding disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in muscle expression of glucose transporter type 4 (GLUT4) | 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 glycerol transporters | 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 expression of fatty acid translocase (FAT/CD36) | 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 |
| Change in muscle expression of fatty acid transporter 4 (FATP4) | 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 expression of muscle fatty acid binding protein (FABPm) | 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 glycogen content (mmol/kg/h) | 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 triglycerides content | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Comparing gylcerol rate of appearance during rest, exercise and recovery in the two groups |
| 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 | Comparing gylcerol rate of disappearance during rest, exercise and recovery in the two groups |
| Change in gylcerol concentration | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing gylcerol concentration during rest, exercise and recovery in the two groups |
| 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 | Comparing palmitate rate of appearance during rest, exercise and recovery in the two groups |
| 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 | Comparing palmitate rate of disappearance during rest, exercise and recovery in the two groups |
| Change in palmitate concentration | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing palmitate kinetics during rest, exercise and recovery in the two groups |
| Change in palmitate oxidation | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing palmitate oxidation during rest, exercise and recovery in the two groups |
| Change in intramuscular palmitate content | Measured at 0, 120, 180 and 360 minutes | Comparing intramuscular palmitate content during rest, exercise and recovery in the two groups |
| Change in palmitate enrichment in intramuscular triglycerides | Measured at 0, 120, 180 and 360 minutes | Comparing palmitate enrichment in intramuscular triglycerides during rest, exercise and recovery in the two groups |
| Change in intramuscular triglycerides fractional synthesis rate | Measured at 0, 120, 180 and 360 minutes | Comparing intramuscular triglycerides fractional synthesis rate during rest, exercise and recovery in the two groups |
| Change in haemoglobin | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing haemoglobin during rest, exercise and recovery in the two groups |
| Change in haematocrit | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing haematocrit during rest, exercise and recovery in the two groups |
| Change in differential blood count | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing differential blood count during rest, exercise and recovery in the two groups |
| Change in plasma IL-6 concentration | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing plasma IL-6 concentration during rest, exercise and recovery in the two groups |
| Change in plasma TNF-alpha concentration | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing plasma TNF-alpha concentration during rest, exercise and recovery in the two groups |
| Change in plasma IL-8 concentration | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing plasma IL-8 concentration during rest, exercise and recovery in the two groups |
| Change in plasma IL-10 concentration | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing plasma IL-10 concentration during rest, exercise and recovery in the two groups |
| Change in plasma IL-1beta concentration | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing plasma IL-1beta concentration during rest, exercise and recovery in the two groups |
| Change in plasma IL-1Ra concentration | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing plasma IL-1Ra concentration during rest, exercise and recovery in the two groups |
| Change in plasma IL-4 concentration | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing plasma IL-4 concentration during rest, exercise and recovery in the two groups |
| Change in plasma sIL-6R concentration | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing plasma sIL-6R concentration during rest, exercise and recovery in the two groups |
| Change in insulin | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing insulin during rest, exercise and recovery in the two groups |
| Change in glucagon | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing glucagon during rest, exercise and recovery in the two groups |
| Change in growth hormone (GH) | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing GH during rest, exercise and recovery in the two groups |
| Change in adrenaline | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing adrenaline during rest, exercise and recovery in the two groups |
| Change in noradrenaline | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing noradrenaline during rest, exercise and recovery in the two groups |
| Change in cortisol | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing cortisol during rest, exercise and recovery in the two groups |
| 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 | Comparing total GLP-1 during rest, exercise and recovery in the two groups |
| Change in active GLP-1 | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing active GLP-1 during rest, exercise and recovery in the two groups |
| Change in gastric inhibitory peptide (GIP) | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing GIP during rest, exercise and recovery in the two groups |
| Change in peptide YY (PYY) | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing PYY during rest, exercise and recovery in the two groups |
| Change in leptin | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing leptin during rest, exercise and recovery in the two groups |
| Change in triglycerides | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing triglycerides during rest, exercise and recovery in the two groups |
| Change in c-peptide | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing c-peptide during rest, exercise and recovery in the two groups |
| 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 | Comparing glucose rate of appearance during exercise and recovery in the two groups |
| 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 | Comparing glucose rate of disappearance during exercise and recovery in the two groups |
| Change in glucose concentration | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes | Comparing glucose concentration during exercise and recovery in the two groups |
| Change in glucose enrichment in intramuscular glycogen | Measured at 0, 120, 180 and 360 minutes | Comparing glucose enrichment in intramuscular glycogen during rest, exercise and recovery in the two groups |
| Change in intramuscular glucose concentration | Measured at 0, 120, 180 and 360 minutes | Comparing intramuscular glucose concentration during rest, exercise and recovery in the two groups |
| Change in glycogen fractional synthesis rate | Measured at 0, 120, 180 and 360 minutes | Comparing intramuscular glycogen fractional synthesis rate during rest, exercise and recovery in the two groups |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in muscle total antioxidant capacity (TAC) | Measured in muscle biopsies taken at 0, 120 and 360 minutes | Comparing muscle total antioxidant capacity (TAC) at rest, after exercise and recovery in the two groups |
| Excess post-exercise oxygen consumption | Measured at -130, 0, 60, 120, 180, 240, 300 and 360 minutes | Comparing excess post-exercise oxygen consumption between the two groups |
| Change in muscle superoxide levels (SOD) | Measured in muscle biopsies taken at 0, 120 and 360 minutes | Comparing muscle superoxide levels (SOD) at rest, after exercise and recovery in the two groups |
Countries
Denmark
Outcome results
None listed