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

Glycogen Depletion Clinical Trial

— REX-6  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05349149
• Other study ID #: H-21063697
• Status: Completed
• Phase: N/A
• Start date: April 20, 2022
• Est. completion date: October 11, 2022

Study information

• Verified date: October 2022
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 11, 2022
• Est. primary completion date: October 11, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Glycogen Depletion

Intervention

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
• 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

Locations

Country	Name	City	State
Denmark	Centre for Physical Activity Research, Rigshospitalet Section 7641	Copenhagen	Capital Region

Sponsors (1)

Lead Sponsor	Collaborator
Helga Ellingsgaard

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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