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

NCT05349149 | Completed

• 1 other identifier: H-21063697
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Glycogen Depletion

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (40)

• 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 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 glucose concentration

  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

  Measured at 0, 120, 180 and 360 minutes

• Change in intramuscular glucose concentration

  Measured at 0, 120, 180 and 360 minutes

Other Outcomes (3)

• Change in muscle total antioxidant capacity (TAC)

  Measured in muscle biopsies taken at 0, 120 and 360 minutes

• Change in muscle superoxide levels (SOD)

  Measured in muscle biopsies taken at 0, 120 and 360 minutes

• Excess post-exercise oxygen consumption

  Measured at -130, 0, 60, 120, 180, 240, 300 and 360 minutes

Study Arms (2)

Tocilizumab

EXPERIMENTAL

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)

Saline

PLACEBO COMPARATOR

As placebo, participants will receive one 30 min intravenous infusion of 100 mL 0.9% saline.

Drug: Saline 9%

Interventions

Tocilizumab/Actemra® (Roche) DRUG

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

Tocilizumab

Saline 9% DRUG

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

Saline

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Eligibility is NOT based on self-representation of gender identity
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Helga Ellingsgaard: lead

Study Sites (1)

Centre for Physical Activity Research, Rigshospitalet Section 7641

Copenhagen, Capital Region, 2100, Denmark

Location

Related Publications (1)

• Kistner TM, Trinh B, Mfeketo K, van Hall G, Pedersen BK, Lieberman DE, Ellingsgaard H. Myokine IL-6 activity enhances post-exercise fatty acid accumulation in skeletal muscle but does not affect glycogen resynthesis. Mol Metab. 2026 Jan;103:102283. doi: 10.1016/j.molmet.2025.102283. Epub 2025 Nov 14.

  PMID: 41242537 DERIVED

MeSH Terms

Interventions

tocilizumab

Study Officials

• Bente K Pedersen, MD

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigators will be blinded to the infusion of saline or tocilizumab
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD, Group leader, Centre for Physical Activity Research

Model Details: Randomized, placebo-controlled, double-blind

Study Record Dates

• First Submitted: April 6, 2022
• First Posted: April 27, 2022
• Study Start: April 20, 2022
• Primary Completion: October 11, 2022
• Study Completion: October 11, 2022
• Last Updated: October 26, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)