Clinical trial NCT05349149: IL-6 Regulation of Energy Stores During Recovery From an Acute Exercise Bout
Official title: Role of IL-6 in Regulating Energy Stores During Recovery From an Acute Exercise Bout
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glycogen Depletion
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2022-04-27
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, placebo-controlled, double-blind
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in muscle glycogen content (mmol/kg/h)
timeFrame: Measured at 0, 120, 180 and 360 minutes
measure: Change in muscle triglycerides content
timeFrame: Measured at 0, 120, 180 and 360 minutes
measure: Change in muscle expression of glucose transporter type 4 (GLUT4)
timeFrame: Measured at 0, 120 and 360 min
measure: Change in muscle expression of fatty acid translocase (FAT/CD36)
timeFrame: Measured at 0, 120 and 360 min
measure: Change in muscle expression of muscle fatty acid binding protein (FABPm)
timeFrame: Measured at 0, 120 and 360 min
measure: Change in muscle expression of fatty acid transporter 4 (FATP4)
timeFrame: Measured at 0, 120 and 360 min
measure: Change in muscle expression of glycerol transporters
timeFrame: Measured at 0, 120 and 360 min
Secondary outcomes:
measure: Change in glucose rate of appearance
timeFrame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in glucose rate of disappearance
timeFrame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in glucose concentration
timeFrame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in glucose enrichment in intramuscular glycogen
timeFrame: Measured at 0, 120, 180 and 360 minutes
measure: Change in intramuscular glucose concentration
timeFrame: Measured at 0, 120, 180 and 360 minutes
measure: Change in glycogen fractional synthesis rate
timeFrame: Measured at 0, 120, 180 and 360 minutes
measure: Change in gylcerol rate of appearance
timeFrame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in gylcerol rate of disappearance
timeFrame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in gylcerol concentration
timeFrame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in palmitate rate of appearance
timeFrame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in palmitate rate of disappearance
timeFrame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in palmitate concentration
timeFrame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in palmitate oxidation
timeFrame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in intramuscular palmitate content
timeFrame: Measured at 0, 120, 180 and 360 minutes
measure: Change in palmitate enrichment in intramuscular triglycerides
timeFrame: Measured at 0, 120, 180 and 360 minutes
measure: Change in intramuscular triglycerides fractional synthesis rate
timeFrame: Measured at 0, 120, 180 and 360 minutes
measure: Change in haemoglobin
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in haematocrit
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in differential blood count
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in plasma IL-6 concentration
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in plasma TNF-alpha concentration
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in plasma IL-8 concentration
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in plasma IL-10 concentration
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in plasma IL-1beta concentration
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in plasma IL-1Ra concentration
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in plasma IL-4 concentration
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in plasma sIL-6R concentration
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in insulin
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in c-peptide
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in glucagon
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in growth hormone (GH)
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in adrenaline
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in noradrenaline
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in cortisol
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in total glucagon-like peptide-1 (GLP-1)
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in active GLP-1
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in gastric inhibitory peptide (GIP)
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in peptide YY (PYY)
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in leptin
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
measure: Change in triglycerides
timeFrame: Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes
Other outcomes:
measure: Change in muscle total antioxidant capacity (TAC)
timeFrame: Measured in muscle biopsies taken at 0, 120 and 360 minutes
measure: Change in muscle superoxide levels (SOD)
timeFrame: Measured in muscle biopsies taken at 0, 120 and 360 minutes
measure: Excess post-exercise oxygen consumption
timeFrame: Measured at -130, 0, 60, 120, 180, 240, 300 and 360 minutes
Locations:
city: Copenhagen
country: Denmark
facility: Centre for Physical Activity Research, Rigshospitalet Section 7641
state: Capital Region
Study officials:
affiliation: Rigshospitalet, Denmark
name: Bente K Pedersen, MD
role: STUDY_CHAIR
References: