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AzTrials

ObesityNCT03967691

IL-6 Regulation of Substrate Metabolism and Influence of Obesity

A study testing Tocilizumab infusion and Saline 0.9% in people with Obesity and Healthy, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 years, men onlyHealthy volunteers can take part
Conditions the study is for
Obesity, Healthy
What is being tested?
Tocilizumab infusion and Saline 0.9%
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
22 participants
Where
1 siteDenmark
Study dates
12 Jun 2019to 3 Apr 2020
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

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

Who cannot join

  • Smoking
  • Severe thyroid or heart disease
  • inflammatory diseases
  • current infection
  • liver disease
  • kidney disease
Show all 17Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Denmark1 site

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

    Copenhagen, 2100

Other trials in Denmark

About this study

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.

Read the detailed description

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
Obesity, Healthy
Being tested
Tocilizumab infusion, Saline 0.9%
Keywords
Interleukin-6, Tocilizumab, Exercise, Substrate Metabolism, Lipolysis
Medical subject headings
Obesity, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tocilizumab infusionDrug

    Also called RoActemra

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

  • Saline 0.9%Drug

    Also called Saline

    100 ml NaCl 0.9% will be infused over 1 hour

Study groups in NCT03967691
Study groupRoleWhat they receive
Saline infusionPlacebo comparatorSubjects will be infused with saline (placebo) on study day 1
Receives: Drug: Saline 0.9%
Tocilizumab infusionActive comparatorSubjects will be infused with tocilizumab on study day 2
Receives: Drug: Tocilizumab infusion
Saline infusion under tocilizumab influenceOtherSubjects will be infused withsaline (but still under the influence of tocilizumab) on study day 3
Receives: Drug: Saline 0.9%

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 0-28 days

Secondary outcomes (14)

  1. Glucose kinetics

    Rate of appearance and disappearance of glucose during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  2. Protein metabolism

    Rate of appearance and disappearance of phenylalanine and tyrosine during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  3. Respiratory exchange ratio (RER)

    RER during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  4. Perceived exhaustion during exercise

    Borg scale (rate of perceived exertion during exercise; score range from minimum 6 to maximum 20; 6 = "no feeling of exertion", 20 = "very, very hard") in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  5. Glucose

    Change in glucose during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  6. Insulin

    Changes in insulin during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  7. C-peptide

    Change in c-peptide during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  8. Glucagon

    Change in glucagon during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  9. Cortisol

    Change in cortisol during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  10. Adrenaline

    Change in adrenaline during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  11. Noradrenaline

    Changes in noradrenaline during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  12. Interleukin 6

    Change in IL-6 during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  13. Free fatty acids

    Change in free fatty acids during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

  14. Triglycerides

    Changes in triglycerides during rest and exercise in the presence of tocilizumab as compared to placebo

    Measured: 0-28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2019
  2. Study start12 Jun 2019
  3. Primary completion3 Apr 2020
  4. Study completion3 Apr 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Crossover
Model description
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.
Masking
Single blind
Who is masked
Participant
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03967691
Sponsor's protocol ID
TOSS
Status last verified
Oct 2020
First submitted
22 May 2019
Last updated
8 Oct 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 35442403

  • 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.

    PubMed 34622233

Questions about this trial

What is this clinical trial studying?

A study testing Tocilizumab infusion and Saline 0.9% in people with Obesity and Healthy, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Lipolytic rate (time frame: 0-28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03967691, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.

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