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IL-6 Regulation of Energy Stores During Recovery From an Acute Exercise Bout

Not Applicable
Completed
Conditions
Glycogen Depletion
Interventions
Drug: Saline 9%
Drug: Tocilizumab/Actemra® (Roche)
Registration Number
NCT05349149
Lead Sponsor
Helga Ellingsgaard
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
30
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SalineSaline 9%As placebo, participants will receive one 30 min intravenous infusion of 100 mL 0.9% saline.
TocilizumabTocilizumab/Actemra® (Roche)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.
Primary Outcome Measures
NameTimeMethod
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 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 expression of glycerol transportersMeasured 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 contentMeasured 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)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)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

Secondary Outcome Measures
NameTimeMethod
Change in glucose enrichment in intramuscular glycogenMeasured at 0, 120, 180 and 360 minutes

Comparing glucose enrichment in intramuscular glycogen during rest, exercise and recovery in the two groups

Change in palmitate concentrationMeasured 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 enrichment in intramuscular triglyceridesMeasured 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 rateMeasured at 0, 120, 180 and 360 minutes

Comparing intramuscular triglycerides fractional synthesis rate during rest, exercise and recovery in the two groups

Change in plasma IL-8 concentrationMeasured 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-4 concentrationMeasured 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 glycogen fractional synthesis rateMeasured at 0, 120, 180 and 360 minutes

Comparing intramuscular glycogen fractional synthesis rate during rest, exercise and recovery in the two groups

Change in glucose rate of appearanceMeasured 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 gylcerol rate of appearanceMeasured 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 palmitate rate of appearanceMeasured 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 plasma IL-6 concentrationMeasured 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 IL-1beta concentrationMeasured 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 concentrationMeasured 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 insulinMeasured 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 glucose rate of disappearanceMeasured 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 intramuscular glucose concentrationMeasured at 0, 120, 180 and 360 minutes

Comparing intramuscular glucose concentration during rest, exercise and recovery in the two groups

Change in palmitate rate of disappearanceMeasured 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 plasma IL-10 concentrationMeasured 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 glucose concentrationMeasured 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 intramuscular palmitate contentMeasured at 0, 120, 180 and 360 minutes

Comparing intramuscular palmitate content during rest, exercise and recovery in the two groups

Change in gylcerol rate of disappearanceMeasured 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 concentrationMeasured 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 oxidationMeasured 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 haemoglobinMeasured 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 haematocritMeasured 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 countMeasured 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 TNF-alpha concentrationMeasured 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 c-peptideMeasured 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 triglyceridesMeasured 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 plasma sIL-6R concentrationMeasured 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 noradrenalineMeasured 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 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 glucagonMeasured 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 adrenalineMeasured 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 cortisolMeasured 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 active GLP-1Measured 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 leptinMeasured 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 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

Trial Locations

Locations (1)

Centre for Physical Activity Research, Rigshospitalet Section 7641

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Copenhagen, Capital Region, Denmark

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