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

Role of IL-6 in Regulating Energy Stores During Recovery From an Acute Exercise Bout

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.

Study Overview

• Status: Completed
• Conditions: Glycogen Depletion
• Intervention / Treatment: Drug: Tocilizumab/Actemra® (Roche); Drug: Saline 9%

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Capital Region
    • Copenhagen, Capital Region, Denmark, 2100
      • Centre for Physical Activity Research, Rigshospitalet Section 7641

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Tocilizumab/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
Placebo Comparator: Saline; As placebo, participants will receive one 30 min intravenous infusion of 100 mL 0.9% saline.	Drug: Saline 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle glycogen content (mmol/kg/h)	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	Measured at 0, 120, 180 and 360 minutes
Change in muscle triglycerides content	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	Measured at 0, 120, 180 and 360 minutes
Change in muscle expression of glucose transporter type 4 (GLUT4)	Comparing muscle expression of GLUT4 before and immediately after exercise and 4 hours after recovery in the two groups	Measured at 0, 120 and 360 min
Change in muscle expression of fatty acid translocase (FAT/CD36)	Comparing muscle expression of FAT/CD36 before and immediately after exercise and 4 hours after recovery in the two groups	Measured at 0, 120 and 360 min
Change in muscle expression of muscle fatty acid binding protein (FABPm)	Comparing muscle expression of FABPm before and immediately after exercise and 4 hours after recovery in the two groups	Measured at 0, 120 and 360 min
Change in muscle expression of fatty acid transporter 4 (FATP4)	Comparing muscle expression of FATP4 before and immediately after exercise and 4 hours after recovery in the two groups	Measured at 0, 120 and 360 min
Change in muscle expression of glycerol transporters	Comparing muscle expression of glycerol transporters before and immediately after exercise and 4 hours after recovery in the two groups	Measured at 0, 120 and 360 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in glucose rate of appearance	Comparing glucose rate of appearance during exercise and recovery in the two groups	Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in glucose rate of disappearance	Comparing glucose rate of disappearance during exercise and recovery in the two groups	Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in glucose concentration	Comparing glucose concentration during exercise and recovery in the two groups	Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in glucose enrichment in intramuscular glycogen	Comparing glucose enrichment in intramuscular glycogen during rest, exercise and recovery in the two groups	Measured at 0, 120, 180 and 360 minutes
Change in intramuscular glucose concentration	Comparing intramuscular glucose concentration during rest, exercise and recovery in the two groups	Measured at 0, 120, 180 and 360 minutes
Change in glycogen fractional synthesis rate	Comparing intramuscular glycogen fractional synthesis rate during rest, exercise and recovery in the two groups	Measured at 0, 120, 180 and 360 minutes
Change in gylcerol rate of appearance	Comparing gylcerol rate of appearance during rest, exercise and recovery in the two groups	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 disappearance	Comparing gylcerol rate of disappearance during rest, exercise and recovery in the two groups	Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in gylcerol concentration	Comparing gylcerol concentration during rest, exercise and recovery in the two groups	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	Comparing palmitate rate of appearance during rest, exercise and recovery in the two groups	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 disappearance	Comparing palmitate rate of disappearance during rest, exercise and recovery in the two groups	Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in palmitate concentration	Comparing palmitate kinetics during rest, exercise and recovery in the two groups	Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in palmitate oxidation	Comparing palmitate oxidation during rest, exercise and recovery in the two groups	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	Comparing intramuscular palmitate content during rest, exercise and recovery in the two groups	Measured at 0, 120, 180 and 360 minutes
Change in palmitate enrichment in intramuscular triglycerides	Comparing palmitate enrichment in intramuscular triglycerides during rest, exercise and recovery in the two groups	Measured at 0, 120, 180 and 360 minutes
Change in intramuscular triglycerides fractional synthesis rate	Comparing intramuscular triglycerides fractional synthesis rate during rest, exercise and recovery in the two groups	Measured at 0, 120, 180 and 360 minutes
Change in haemoglobin	Comparing haemoglobin during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in haematocrit	Comparing haematocrit during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in differential blood count	Comparing differential blood count during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in plasma IL-6 concentration	Comparing plasma IL-6 concentration during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in plasma TNF-alpha concentration	Comparing plasma TNF-alpha concentration during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in plasma IL-8 concentration	Comparing plasma IL-8 concentration during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in plasma IL-10 concentration	Comparing plasma IL-10 concentration during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in plasma IL-1beta concentration	Comparing plasma IL-1beta concentration during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in plasma IL-1Ra concentration	Comparing plasma IL-1Ra concentration during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in plasma IL-4 concentration	Comparing plasma IL-4 concentration during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in plasma sIL-6R concentration	Comparing plasma sIL-6R concentration during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in insulin	Comparing insulin during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in c-peptide	Comparing c-peptide during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in glucagon	Comparing glucagon during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in growth hormone (GH)	Comparing GH during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in adrenaline	Comparing adrenaline during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in noradrenaline	Comparing noradrenaline during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in cortisol	Comparing cortisol during rest, exercise and recovery in the two groups	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)	Comparing total GLP-1 during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in active GLP-1	Comparing active GLP-1 during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in gastric inhibitory peptide (GIP)	Comparing GIP during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in peptide YY (PYY)	Comparing PYY during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in leptin	Comparing leptin during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Change in triglycerides	Comparing triglycerides during rest, exercise and recovery in the two groups	Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle total antioxidant capacity (TAC)	Comparing muscle total antioxidant capacity (TAC) at rest, after exercise and recovery in the two groups	Measured in muscle biopsies taken at 0, 120 and 360 minutes
Change in muscle superoxide levels (SOD)	Comparing muscle superoxide levels (SOD) at rest, after exercise and recovery in the two groups	Measured in muscle biopsies taken at 0, 120 and 360 minutes
Excess post-exercise oxygen consumption	Comparing excess post-exercise oxygen consumption between the two groups	Measured at -130, 0, 60, 120, 180, 240, 300 and 360 minutes

Collaborators and Investigators

• Sponsor: Helga Ellingsgaard
• Investigators: Study Chair: Bente K Pedersen, MD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2022
• Primary Completion (Actual): October 11, 2022
• Study Completion (Actual): October 11, 2022

Study Registration Dates

• First Submitted: April 6, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 27, 2022

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: H-21063697

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No