Ectopic Adipose Tissue, Exercise Training and IL-6
Condition: Adiposity
MeSH terms: Obesity
Study type: Interventional

Summary: 
      Aim: Exercise training improves the risk of cardiometabolic diseases; yet the underlying
      mechanisms are unclear. Exercise induces release of IL-6 from skeletal muscle. Acute
      elevations in IL-6 improve lipid and glucose metabolism, the latter partly through a delayed
      gastric emptying. Physical inactivity causes accumulation of visceral fat (VAT). Visceral and
      epicardial adipose tissue (EAT) is more inflamed than subcutaneous adipose tissue. Thus, the
      investigators hypothesize that exercise-induced IL-6 mediates the exercise-induced reduction
      in EAT and VAT. Secondly, the investigators hypothesize that exercise-induced adaptations in
      glucose metabolism and gastric motility are dependent on IL-6. Finally the investigators
      hypothesise that both endurance and resistance exercise training reduce VAT and EAT.

      Primary aim: To investigate the effects of exercise training on VAT and to determine to what
      extend IL-6 mediates this effect.

      Secondary aims: 1) To determine whether 12 weeks of endurance and strength training can
      reduce the amount of EAT. 2) To study whether the effects of exercise on glucose metabolism
      and gastric emptying are dependent on IL-6.

      Methods: Inclusion: 70 inactive men and women, >18 years, waist to height ratio > 0.5 and/or
      waist circumference ≥ 88 cm (women); waist circumference ≥ 102 cm (men) Design: A 12-week,
      double-blinded randomised, placebo-controlled exercise intervention study.

      Intervention: Subjects will be randomised to one of five groups: i) Tocilizumab (IL-6
      receptor antibody) and endurance training, ii) Placebo to Tocilizumab and endurance training,
      iii) Tocilizumab, no exercise iv) Placebo to Tocilizumab and no training, and v) Placebo to
      Tocilizumab, and resistance training. Tocilizumab/placebo dose will be administered
      (according to standard recommendations) before the first training session, and maintained
      during the 12-week training program. Training will be supervised to ensure intensity and
      compliance. Subjects will be instructed not to change eating habits and informed that this
      study does not aim for a weight loss.

      Statistical considerations: Study investigators are blinded to treatment allocation. Dropouts
      will be replaced. A sample size of 70 subjects is needed to detect a 10% change in visceral
      adipose, with a power of 80% and a significance level of 0.05.
    


Intervention name(s): Endurance Exercise Training; Resistance Exercise Training; No Exercise; Tocilizumab; Placebo
Intervention type(s): Behavioral; Behavioral; Behavioral; Drug; Drug
Intervention description(s): Three months of supervised training. Interval training, 3 sessions weekly of 45 min. During intervals the intensity will be minimum 70 % of VO2 max; Three months of supervised resistance training. Subjects will perform 3 weekly sessions of 45 min. The intensity will be kept at minimum 60% of 1RM.; Control to exercise; Tocilizumab infusion will be administered monthly (8 mg/kg body weight i.v., maximun 800 mg). Each subject will receive 3 infusions during the study period.; Saline infusion will be administered monthly (same volume as Tocilizumab). Each subject will receive 3 infusions during the study period.
Other intervention name(s): Endurance exercise; Resistance exercise; RoActemra; Saline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other