The role of exercise combined with tocilizumab in visceral and epicardial adipose tissue and gastric emptying rate in abdominally obese participants: protocol for a randomised controlled trial

Trials. 2018 May 2;19(1):266. doi: 10.1186/s13063-018-2637-0.

Abstract

Background: Exercise reduces the amount of visceral adipose tissue (VAT) and the risk of cardiometabolic diseases. The underlying mechanisms responsible for these exercise-induced adaptations are unclear, but they may involve lipolytic actions of interleukin-6 (IL-6). Contracting skeletal muscles secrete IL-6, leading to increased circulating IL-6 levels in response to exercise. The aim of this study is to investigate whether IL-6 is involved in mediating the effects of exercise on visceral and epicardial adipose tissue volume and glycaemic control.

Methods/design: Seventy-five physically inactive males and females aged > 18 years with a waist-to-height ratio > 0.5 and/or waist circumference ≥ 88 cm (females) or ≥ 102 cm (males) are being recruited to participate in a 12-week intervention study. Participants are randomly allocated to one of five groups (1:1:1:1:1). Two groups consist of supervised endurance exercise training combined with the IL-6 blocker tocilizumab (ET) or saline used as placebo (EP), two groups consist of no exercise combined with tocilizumab (NT) or placebo (NP), and one group consists of resistance exercise and placebo (RP). Although the study is an exploratory trial, the primary outcome is change in VAT volume from before to after intervention, with secondary outcomes being changes in (1) epicardial adipose tissue, (2) pericardial adipose tissue and (3) gastric emptying. Depots of adipose tissue are quantitated by magnetic resonance imaging Gastric emptying and glucose metabolism are assessed using mixed-meal tolerance tests.

Discussion: Understanding the role of IL-6 in mediating the effects of exercise on visceral and epicardial adipose tissue and glycaemic control may lead to novel therapeutic approaches in the prevention of cardiometabolic diseases.

Trial registration: ClinicalTrials.gov, NCT02901496 . Registered on 1 August 2016 and posted retrospectively on 15 September 2016.

Keywords: Epicardial adipose tissue; Exercise; Gastric emptying rate; Glucose homeostasis; Interleukin-6; Visceral adipose tissue.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Denmark
  • Female
  • Gastric Emptying / drug effects*
  • Humans
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / metabolism
  • Intra-Abdominal Fat / drug effects*
  • Intra-Abdominal Fat / metabolism
  • Intra-Abdominal Fat / physiopathology
  • Male
  • Middle Aged
  • Obesity, Abdominal / blood
  • Obesity, Abdominal / diagnosis
  • Obesity, Abdominal / physiopathology
  • Obesity, Abdominal / therapy*
  • Physical Endurance
  • Randomized Controlled Trials as Topic
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Receptors, Interleukin-6 / metabolism
  • Resistance Training*
  • Time Factors
  • Treatment Outcome
  • Waist Circumference
  • Waist-Height Ratio
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Blood Glucose
  • IL6 protein, human
  • IL6R protein, human
  • Interleukin-6
  • Receptors, Interleukin-6
  • tocilizumab

Associated data

  • ClinicalTrials.gov/NCT02901496