Ectopic Adipose Tissue, Exercise Training and IL-6

NCT02901496 | Completed

• 1 other identifier: H-16018062
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Changes in visceral fat mass

  Visceral fat mass will be measured by MRI before and after the intervention. Difference in change in visceral fat mass from baseline to 12 weeks follow up will be compared between group: Endurancetraining + tocilizumab and group: Endurancetraining + placebo.

  0, 12 weeks

Secondary Outcomes (7)

• Changes in visceral fat mass

  0, 12 weeks

• Changes in visceral fat mass

  0, 12 weeks

• Changes in visceral fat mass

  0, 12 weeks

• Changes in visceral fat mass

  0, 12 weeks

• Changes in visceral fat mass

  0, 12 weeks

Other Outcomes (44)

• Peri- and paracardial adipose tissue volume (measured by MRI)

  0, 12 weeks

• Body composition analysis (measured by Dual-energy X-ray absorptiometry)

  0, 4, 8 and 12 weeks

• Waist circumference (measured in cm)

  0, 4, 8 and 12 weeks

Study Arms (5)

Endurance exercise + infusion of Tocilizumab

EXPERIMENTAL

Endurance exercise training + monthly infusion of Tocilizumab

Behavioral: Endurance Exercise Training; Drug: Tocilizumab

Endurance exercise + infusion of placebo

EXPERIMENTAL

Endurance exercise training + monthly infusion of placebo

Behavioral: Endurance Exercise Training; Drug: Placebo

No exercise + infusion of Tocilizumab

EXPERIMENTAL

No exercise + monthly infusion of Tocilizumab

Behavioral: No Exercise; Drug: Tocilizumab

No exercise + infusion of placebo

PLACEBO COMPARATOR

No exercise training + monthly infusion of placebo

Behavioral: No Exercise; Drug: Placebo

Resistance exercise + infusion of placebo

EXPERIMENTAL

Resistance exercise training + monthly infusion of placebo

Behavioral: Resistance Exercise Training; Drug: Placebo

Interventions

Endurance Exercise Training BEHAVIORAL

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

Also known as: Endurance exercise

Endurance exercise + infusion of Tocilizumab; Endurance exercise + infusion of placebo

Resistance Exercise Training BEHAVIORAL

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.

Also known as: Resistance exercise

Resistance exercise + infusion of placebo

No Exercise BEHAVIORAL

Control to exercise

No exercise + infusion of Tocilizumab; No exercise + infusion of placebo

Tocilizumab DRUG

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.

Also known as: RoActemra

Endurance exercise + infusion of Tocilizumab; No exercise + infusion of Tocilizumab

Placebo DRUG

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

Also known as: Saline

Endurance exercise + infusion of placebo; No exercise + infusion of placebo; Resistance exercise + infusion of placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women
• Sedentary
• Waist to height ratio ≥ ½ and/or waist circumference ≥ 88 cm (women); waist circumference ≥ 102 cm (men)
• Age ≥ 18 y

You may not qualify if:

• Pregnancy
• Diagnosed with diabetes (HbA1c ≥ 48 mmol/mol or fasting glucose ≥ 7.0 mmol/l)
• Diagnosed with ischemic heart disease
• Atrial fibrillation
• Treatment with biologic rheumatic drugs, systemic prednisolone or other immunosuppressive treatments
• Health conditions that prevents individuals from participating in the exercise training intervention e.g. severe obesity
• Patients who cannot undergo MRI scans (e.g. kidney disease, metallic implants or claustrophobia)

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

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

Copenhagen, 2100, Denmark

Location

Related Publications (3)

• Wedell-Neergaard AS, Lang Lehrskov L, Christensen RH, Legaard GE, Dorph E, Larsen MK, Launbo N, Fagerlind SR, Seide SK, Nymand S, Ball M, Vinum N, Dahl CN, Henneberg M, Ried-Larsen M, Nybing JD, Christensen R, Rosenmeier JB, Karstoft K, Pedersen BK, Ellingsgaard H, Krogh-Madsen R. Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial. Cell Metab. 2019 Apr 2;29(4):844-855.e3. doi: 10.1016/j.cmet.2018.12.007. Epub 2018 Dec 27.

  PMID: 30595477 RESULT

• Christensen RH, Wedell-Neergaard AS, Lehrskov LL, Legaard GE, Dorph E, Larsen MK, Launbo N, Fagerlind SR, Seide SK, Nymand S, Ball M, Vinum NB, Dahl CN, Henneberg M, Ried-Larsen M, Boesen MP, Christensen R, Karstoft K, Krogh-Madsen R, Rosenmeier JB, Pedersen BK, Ellingsgaard H. Effect of Aerobic and Resistance Exercise on Cardiac Adipose Tissues: Secondary Analyses From a Randomized Clinical Trial. JAMA Cardiol. 2019 Aug 1;4(8):778-787. doi: 10.1001/jamacardio.2019.2074.

  PMID: 31268469 DERIVED

• Christensen RH, Wedell-Neergaard AS, Lehrskov LL, Legard GE, Dorph EB, Nymand S, Ball MK, Zacho M, Christensen R, Ellingsgaard H, Rosenmeier JB, Krogh-Madsen R, Pedersen BK, Karstoft K. 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.

  PMID: 29720225 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Resistance Training; tocilizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Bente K Pedersen, Professor

  Rigshospitalet, Denmark

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD student

Study Record Dates

• First Submitted: August 1, 2016
• First Posted: September 15, 2016
• Study Start: August 1, 2016
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: February 26, 2024

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)