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Completed

NCT Number: NCT03967691

IL-6 Regulation of Substrate Metabolism and Influence of Obesity

The aim of the study is to investigate the effects of blocking IL-6 signaling with tocilizumab on lipid, glucose and protein metabolism during rest and exercise in healthy and obese humans.

Interleukin-6 is a molecule produced by a variety of cells and impacts on energy metabolism during fasting and fed conditions. Systemic IL-6 levels are low but increase acutely in response to fasting, exercise and infection, and also chronically in response to obesity and other conditions of lowgrade inflammation.Our recent human intervention study showed that IL-6 receptor blockade prevents exercise training from reducing visceral fat mass.

Whether IL-6 receptor blockade directly regulates lipolysis and/or lipid oxidation in humans is however unclear. Therefore, this study will be performed to investigate the physiological role of IL-6 on lipid, glucose and protein metabolism in humans.

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Key information

Conditions

Obesity Behavior Body Weight Healthy Motor Activity Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–60 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Rigshospitalet, Centre of Inflammation and Metabolism (CIM) Centre for Physical Activity Research (CFAS)

Copenhagen, 2100, Denmark

About this study

The aim of the study is to assess changes in substrate kinetics, that is, lipolytic rate, rate of appearance and disappearance of free fatty acids, fatty acid oxidation, glucose rate of appearance and disappearance and protein synthesis and degradation during rest and exercise with and without IL-6 receptor blockade. We will assess the acute effects of blocking IL-6 as well as the long-term consequences of IL-6 receptor blockade on all the above parameters.

Overall, we hypothesize that blocking IL-6 changes substrate kinetics. More specifically we hypothesize that blocking IL-6 reduces the appearance of free fatty acids, reduces the lipolytic rate and lipid oxidation. We hypothesize that the consequences of blocking IL-6 will be observed during resting and exercising conditions and both immediately and longterm after IL-6 receptor blockade. We hypothesize that IL-6 receptor blockade results in an increased respiratory exchange ratio (RER) and thus increased reliance on glucose as substrate.

In this study 10 healthy males and 10 obese males will be included. Subjects will be infused with saline on 2 of the study days and tocilizumab on 1 of the study days.

Isotope dilution techniques with [6,6-2H2]Glucose, [1,1,2,3,3-D5]glycerol, K-[U-13C16]palmitate, L-[ring-D5]phenylalanine, L-[D2]tyrosine will be applied to assess lipid, glucose and protein kinetics. Respiratory exchange ratio will be measured by indirect calorimetry. The BORG scale will be used to assess the perceived exertion during exercise.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • BMI < 18 and > 25 kg/m2 or ≥ 30 and ≤ 40 kg/m2
  • Healthy (based on screening)

Exclusion criteria

  • Smoking
  • Severe thyroid or heart disease
  • inflammatory diseases
  • current infection
  • liver disease
  • kidney disease
  • immunosuppressive disease
  • corticosteroid use
  • regular NSAID usage
  • aspirin use >100 mg/d
  • history of carcinoma
  • history of tuberculosis
  • anemia
  • neutropenia
  • low platelets
  • bleeding disorders
  • obstructive pulmonary disease

Treatment and study plan

Tocilizumab infusion

Drug

Tocilizumab (8mg/kg body weight diluted to 100 ml NaCl 0.9%) will be infused over 1 hour

Other names: RoActemra

saline 0.9%

Drug

100 ml NaCl 0.9% will be infused over 1 hour

Other names: Saline

Primary outcomes

  1. Lipolytic rate

    Time frame: 0-28 days

    Rate of appearance and disappearance of glycerol and palmitate, fatty acid oxidation during rest and exercise in the presence of tocilizumab as compared to placebo

Secondary outcomes

  1. Glucose kinetics

    Time frame: 0-28 days

    Rate of appearance and disappearance of glucose during rest and exercise in the presence of tocilizumab as compared to placebo

  2. Protein metabolism

    Time frame: 0-28 days

    Rate of appearance and disappearance of phenylalanine and tyrosine during rest and exercise in the presence of tocilizumab as compared to placebo

  3. Respiratory exchange ratio (RER)

    Time frame: 0-28 days

    RER during rest and exercise in the presence of tocilizumab as compared to placebo

  4. Perceived exhaustion during exercise

    Time frame: 0-28 days

    Borg scale (rate of perceived exertion during exercise; score range from minimum 6 to maximum 20; 6 = "no feeling of exertion", 20 = "very, very hard") in the presence of tocilizumab as compared to placebo

  5. Glucose

    Time frame: 0-28 days

    Change in glucose during rest and exercise in the presence of tocilizumab as compared to placebo

  6. Insulin

    Time frame: 0-28 days

    Changes in insulin during rest and exercise in the presence of tocilizumab as compared to placebo

  7. C-peptide

    Time frame: 0-28 days

    Change in c-peptide during rest and exercise in the presence of tocilizumab as compared to placebo

  8. Glucagon

    Time frame: 0-28 days

    Change in glucagon during rest and exercise in the presence of tocilizumab as compared to placebo

  9. Cortisol

    Time frame: 0-28 days

    Change in cortisol during rest and exercise in the presence of tocilizumab as compared to placebo

  10. Adrenaline

    Time frame: 0-28 days

    Change in adrenaline during rest and exercise in the presence of tocilizumab as compared to placebo

  11. Noradrenaline

    Time frame: 0-28 days

    Changes in noradrenaline during rest and exercise in the presence of tocilizumab as compared to placebo

  12. Interleukin 6

    Time frame: 0-28 days

    Change in IL-6 during rest and exercise in the presence of tocilizumab as compared to placebo

  13. Free fatty acids

    Time frame: 0-28 days

    Change in free fatty acids during rest and exercise in the presence of tocilizumab as compared to placebo

  14. Triglycerides

    Time frame: 0-28 days

    Changes in triglycerides during rest and exercise in the presence of tocilizumab as compared to placebo

Sponsors and collaborators

Lead sponsor

Rigshospitalet, Denmark

Other

Registry information

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
May 30, 2019
Registry last updated
Oct 8, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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