Exercise-regulated Organ Crosstalk, Influence of IL-6

NCT06334653 | Completed

• 1 other identifier: H-23069670
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Overall the study investigates organ crosstalk during exercise. More specifically, the study investigates the role of IL-6 in regulating glucose, fatty acid, and amino acid kinetics at whole body level and in skeletal muscle, liver, and brain. Furthermore, the study investigates the uptake and release of extracellular vesicles in skeletal muscle, liver, and brain in reponse to exercise.

Conditions

Healthy Volunteers Only; Energy Metabolism

Keywords

tocilizumab; exercise; IL-6; extracellular vesicles; energy; muscle; liver; brain

Outcome Measures

Primary Outcomes (10)

• Whole body substrate kinetics.

  Comparing rates of appearances (Ra) and disappearances (Rd) of glucose, glycerol, palmitate, amino acids between placebo and IL-6R ab at rest, during exercise, and recovery.

  Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).

• Tissue specific utilization and production of substrates.

  Comparing, between placebo and IL-6Rab, by measuring in plasma, the Ra and Rd of substrates in muscle, liver, and brain at rest, during exercise, and recovery using the non-steady-state equations of Steele adapted for stable isotopes.

  Comparisons between study arms are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).

• IL-6 regulation of protein synthesis and degradation.

  Comparing differences in protein synthesis and degradation rates between placebo and IL-6Rab at rest, during exercise, and during recovery from exercise.

  Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).

• Number of EVs from muscle, liver, and brain.

  Comparing the number of EVs deriving from skeletal muscle, liver, and brain.

  Comparisons between placebo and IL-6R ab are done before exercise (time points 255 and 270 minutes).

• Size of EVs from muscle, liver, and brain.

  Comparing EV size deriving from skeletal muscle, liver, and brain.

  Comparisons between placebo and IL-6R ab are done before exercise (time points 255 and 270 minutes).

• EVs from muscle, liver, and brain.

  Comparing the content of EVs deriving from skeletal muscle, liver, and brain.

  Comparisons between placebo and IL-6R ab are done before exercise (time points 255 and 270 minutes).

• Influence of exercise on EV number.

  Comparing the number of EVs deriving from skeletal muscle, liver, and brain in response to exercise.

  Comparisons between placebo and IL-6R ab are done throughout a 1-hour exercise bout (time points 285, 300, 315, and 330 minutes).

• Influence of exercise on EV size

  Comparing EV size deriving from skeletal muscle, liver, and brain in response to exercise.

  Comparisons between placebo and IL-6R ab are done throughout a 1-hour exercise bout (time points 285, 300, 315, and 330 minutes).

• Influence of exercise on EV content.

  Comparing the content of EVs deriving from skeletal muscle, liver, and brain in response to exercise.

  Comparisons between placebo and IL-6R ab are done throughout a 1-hour exercise bout (time points 285, 300, 315, and 330 minutes).

• Tissue specific proteomic content of EVs.

  Comparing differences in proteomic content of EVs from skeletal muscle, liver, and brain in response to exercise.

  Comparisons between placebo and IL-6R ab are done at the end of a 1-hour exercise bout (330 minutes).

Secondary Outcomes (12)

• Lactate.

  Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).

• Pyruvate.

  Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).

• Keto acids.

  Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).

• Ketone bodies.

  Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).

• Influence of IL-6 on fatty acid oxidation rates.

  Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Saline infusion

Other: exercise

Tocilizumab

EXPERIMENTAL

IL-6 receptor antibody infusion (8 mg/kg body weight, max 800 mg)

Other: exercise

Interventions

exercise OTHER

acute exercise bout

Placebo; Tocilizumab

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Minimum age: 18 years
• Maximum age: 45 years
• Minimum BMI: 18
• Maximum BMI: 25
• Sex: Male
• Healthy (based on screening)
• Stable body weight for 6 months
• VO2max (mL/kg/min) ≥ 50

You may not qualify if:

• Smoking
• Thyroid disease
• Heart disease
• Inflammatory diseases
• Current infection
• Liver disease (transaminases more than 2x upper normal range)
• Kidney disease (creatinine more than1.5 mg/dl)
• Known immunosuppressive disease
• Corticosteroid use
• Regular NSAID or paracetamol usage
• Aspirin use more than 100 mg/d
• History of carcinoma
• History of tuberculosis
• Anemia (hematocrit less than 33%)
• WBC less than 1 x 10\^3

Sponsors & Collaborators

• Helga Ellingsgaard: lead

Study Sites (1)

Rigshospitalet

Copenhagen, Capital Region, 2100, Denmark

Location

MeSH Terms

Conditions

Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Helga Ellingsgaard, PhD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 28, 2024
• Study Start: April 9, 2024
• Primary Completion: June 25, 2024
• Study Completion: June 25, 2024
• Last Updated: October 1, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)