IL-6 Regulation of Substrate Metabolism and Influence of Obesity

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-12

Study Completion Date

2020-04-03

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Targeting the Gut Microbiome to Investigate the Pathways of Progression From Obesity to Metabolic Diseases in an At-risk Population.

NCT01433120

Obesity Insulin Resistance

COMPLETED NA

A Study to Evaluate the Effect of Lipid Infusion on Toll Like Receptor 4 (TLR4) Signaling

NCT01740817

Diabetes Obesity

COMPLETED NA

Evaluation of the Effects of a L.Reuteri Strain on Markers of Inflammation, Cardiovascular Risk and Fatty Liver Disease

NCT02972567

Metabolic Syndrome X

COMPLETED NA

Impact of a High Saturated Fat Diet on Fasted Systemic and White Adipose Tissue Inflammatory Responses

NCT03569189

Inflammation Obesity Inflammatory Response +1 more

COMPLETED NA

B195: Effect of Diet-Induced Energy Deficit and Body Fat Reduction on Inflammatory Markers in Obese Subjects

NCT00302926

Obesity

COMPLETED NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The aim of the study is to assess changes in substrate kinetics, that is, lipolytic rate, rate of appearance and disappearance of free fatty acids, fatty acid oxidation, glucose rate of appearance and disappearance and protein synthesis and degradation during rest and exercise with and without IL-6 receptor blockade. We will assess the acute effects of blocking IL-6 as well as the long-term consequences of IL-6 receptor blockade on all the above parameters.

Overall, we hypothesize that blocking IL-6 changes substrate kinetics. More specifically we hypothesize that blocking IL-6 reduces the appearance of free fatty acids, reduces the lipolytic rate and lipid oxidation. We hypothesize that the consequences of blocking IL-6 will be observed during resting and exercising conditions and both immediately and longterm after IL-6 receptor blockade. We hypothesize that IL-6 receptor blockade results in an increased respiratory exchange ratio (RER) and thus increased reliance on glucose as substrate.

In this study 10 healthy males and 10 obese males will be included. Subjects will be infused with saline on 2 of the study days and tocilizumab on 1 of the study days.

Isotope dilution techniques with \[6,6-2H2\]Glucose, \[1,1,2,3,3-D5\]glycerol, K-\[U-13C16\]palmitate, L-\[ring-D5\]phenylalanine, L-\[D2\]tyrosine will be applied to assess lipid, glucose and protein kinetics. Respiratory exchange ratio will be measured by indirect calorimetry. The BORG scale will be used to assess the perceived exertion during exercise.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Obesity Healthy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

CROSSOVER

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.

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants

Only subjects will be masked regarding order of saline and tocilizumab infusion.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Saline infusion

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

Group Type PLACEBO_COMPARATOR

Saline 0.9%

Intervention Type DRUG

100 ml NaCl 0.9% will be infused over 1 hour

Tocilizumab infusion

Subjects will be infused with tocilizumab on study day 2

Group Type ACTIVE_COMPARATOR

Tocilizumab infusion

Intervention Type DRUG

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

Saline infusion under tocilizumab influence

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

Group Type OTHER

Saline 0.9%

Intervention Type DRUG

100 ml NaCl 0.9% will be infused over 1 hour

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Tocilizumab infusion

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

Intervention Type DRUG

Saline 0.9%

100 ml NaCl 0.9% will be infused over 1 hour

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

RoActemra Saline

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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

Exclusion Criteria

* 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
* bleeding disorders
* obstructive pulmonary disease

Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes