Ectopic Adipose Tissue, Exercise Training and IL-6

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.

Conditions

• Adiposity

Interventions

BEHAVIORAL

Endurance Exercise Training

Three months of supervised training. Interval training, 3 sessions weekly of 45 min. During intervals the intensity will be minimum 70 % of VO2 max

BEHAVIORAL

Resistance Exercise Training

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.

BEHAVIORAL

No Exercise

Control to exercise

DRUG

Tocilizumab

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.

DRUG

Placebo

Saline infusion will be administered monthly (same volume as Tocilizumab). Each subject will receive 3 infusions during the study period.

Sponsors & Collaborators

• Rigshospitalet, Denmark

  lead OTHER

Principal Investigators

• Bente K Pedersen, Professor · Rigshospitalet, Denmark

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-08-31

Primary Completion

2018-04-30

Completion

2018-04-30

Countries

• Denmark

Study Locations