IL-6 Regulation of Substrate Metabolism and Influence of Obesity

NCT03967691 | Completed

• 1 other identifier: TOSS
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity; Healthy

Keywords

Interleukin-6; Tocilizumab; Exercise; Substrate Metabolism; Lipolysis

Outcome Measures

Primary Outcomes (1)

• Lipolytic rate

  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

  0-28 days

Secondary Outcomes (14)

• Glucose kinetics

  0-28 days

• Protein metabolism

  0-28 days

• Respiratory exchange ratio (RER)

  0-28 days

• Perceived exhaustion during exercise

  0-28 days

• Glucose

  0-28 days

Study Arms (3)

Saline infusion

PLACEBO COMPARATOR

Subjects will be infused with saline (placebo) on study day 1

Drug: Saline 0.9%

Tocilizumab infusion

ACTIVE COMPARATOR

Subjects will be infused with tocilizumab on study day 2

Drug: Tocilizumab infusion

Saline infusion under tocilizumab influence

OTHER

Subjects will be infused withsaline (but still under the influence of tocilizumab) on study day 3

Drug: Saline 0.9%

Interventions

Tocilizumab infusion DRUG

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

Also known as: RoActemra

Tocilizumab infusion

Saline 0.9% DRUG

100 ml NaCl 0.9% will be infused over 1 hour

Also known as: Saline

Saline infusion; Saline infusion under tocilizumab influence

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

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 (2)

• Trinh B, Peletier M, Simonsen C, Plomgaard P, Karstoft K, Pedersen BK, van Hall G, Ellingsgaard H. Amino Acid Metabolism and Protein Turnover in Lean and Obese Humans During Exercise-Effect of IL-6 Receptor Blockade. J Clin Endocrinol Metab. 2022 Jun 16;107(7):1854-1864. doi: 10.1210/clinem/dgac239.

  PMID: 35442403 DERIVED

• Trinh B, Peletier M, Simonsen C, Plomgaard P, Karstoft K, Klarlund Pedersen B, van Hall G, Ellingsgaard H. Blocking endogenous IL-6 impairs mobilization of free fatty acids during rest and exercise in lean and obese men. Cell Rep Med. 2021 Sep 9;2(9):100396. doi: 10.1016/j.xcrm.2021.100396. eCollection 2021 Sep 21.

  PMID: 34622233 DERIVED

MeSH Terms

Conditions

Obesity; Motor Activity

Interventions

tocilizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Helga Ellingsgaard, Ph.D.

  CFAS, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Only subjects will be masked regarding order of saline and tocilizumab infusion.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Group leader

Model Details: The study is designed in a placebo-controlled crossover manner, consisting of a screening visit and three study visits/study days. the Subjects will be infused with saline (placebo) on two of the study days and tocilizumab on one of the study days.

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: May 30, 2019
• Study Start: June 12, 2019
• Primary Completion: April 3, 2020
• Study Completion: April 3, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)