Type 2 DiabetesMUSILNCT01771445
Role of Interleukin-1 in the Regulation of Muscle Derived Interleukin-6 During Exercise
A study testing IL-1Ra in people with Type 2 Diabetes, run by Marc Y.Donath at 1 site in Switzerland.
Trial summary
Aim: Evaluate the regulation of muscle derived Interleukin-6 (IL-6)during exercise and in particular whether it is regulated by the Interleukin-1 (IL-1) system. Rationale: It has been shown that IL-1 antagonism improves glycemia and insulin secretion in patients with type 2 Diabetes. Read more about this study
- Who is it for?
- Ages 20 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- IL-1Ra
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteSwitzerland
- Study dates
- Dec 2011to Oct 2013
- 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 20 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- male
- non-smoking
- apparently healthy
- BMI > 18 and < 26kg/m2
- Age 20-50 years
- Regular exercise including a minimum of two runs weekly of a total duration of > 2h
- Willingness to use contraceptive measures adequate to prevent the subject's partner from becoming pregnant during the study. Adequate contraceptive measures include hormonal methods used for two or more cycles prior to Screening (e.g., oral contraceptive pills, contraceptive patch, or contraceptive vaginal ring), double barrier methods (e.g., contraceptive sponge, diaphragm used in conjunction with contraceptive foam or jelly, and condom used in conjunction with contraceptive foam or jelly), intrauterine methods (IUD), sterilization (e.g., tubal ligation or a monogamous relationship with a vasectomized partner), and abstinence.
Who cannot join
- Clinical signs of infection in the week before inclusion or history of infection during the last 3 months (CRP > 5mg/L)
- Impaired fasting glucose (fasting plasma glucose > 5.5mmol/L)
- Hematologic disease (leukocyte count < 1.5x109/L, hemoglobin < 11 g/dL, platelets < 100 x 103/uL)
- Kidney disease (creatinine > 1.5 mg/dL for men and 1.4mg/dL for woman)
- Liver disease (transaminases > 2x upper normal range)
- Heart disease
Show all 15Show fewer
- Pulmonary disease
- Inflammatory disease
- History of carcinoma
- History of tuberculosis
- Alcohol consumption > 40g/d
- Known allergy to Kineret
- Current treatment with any drug in the week before inclusion, including vitamin supplementation (especially vitamin C and E)
- Use of any investigational drug within 30 days prior to enrollment or within 5 half-lives of the investigational drug, whichever is longer
- Subject refusing or unable to give written informed consent
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital of Basel, Division of Endocrinology
Basel, Basel
About this study
Aim: Evaluate the regulation of muscle derived Interleukin-6 (IL-6)during exercise and in particular whether it is regulated by the Interleukin-1 (IL-1) system.
Rationale: It has been shown that IL-1 antagonism improves glycemia and insulin secretion in patients with type 2 Diabetes. However, IL-1 antagonism also decreases IL-6 levels. The effect if IL-6 on the glucose metabolism has been unclear in the past and subject to intense debate, with recent evidence indicating a beneficial role in regulating glucose metabolism. However little is known about regulation of muscle-induced IL-6 produced during exercise. It is therefore our aim to investigate whether exercise induced increases in IL-6 are dependent on the IL-1 system. If IL-1 antagonism does decrease IL-6 and along with it, the beneficial potential of IL-6, this may require additional medication like IL-6 substitution or dipeptidyl peptidase-IV (DPP-IV)antagonists.
In addition, the investigators will assess the effect of IL-1 antagonism on insulin and Glucagon like peptide-1 (GLP-1) secretion as well as muscle soreness,fatigue and vascular function in response to an acute exercise bout.
Read the detailed description
This is a randomized placebo-controlled, double blind, cross-over, proof-of-concept study.
The study will consist of one screening visit followed by 3 study visits. During the first two study visits, the subjects (20 apparently healthy, lean men) will perform a submaximal exercise bout on a treadmill for 60 minutes. Subjects will be randomly assigned into two groups consisting each of 10 subjects receiving study medication in a double-blinded, crossed over manner.
- Conditions
- Type 2 Diabetes
- Being tested
- IL-1Ra, Placebo
- Keywords
- IL-1, IL-6, Inflammation
- Medical subject headings
- Diabetes Mellitus, Type 2, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL-1RaDrug
100mg, s.c, once only
PlaceboDrug
100mg, s.c., once only
| Study group | Role | What they receive |
|---|---|---|
| IL-1Ra | Active comparator | Not described Receives: Drug: IL-1Ra |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
IL6
Measured: Change of IL6 during exercise stimulation at baseline compared to change of IL6 during exercise stimulation at day 7
Secondary outcomes (15)
change of inflammatory markers (CRP, Tumor Necrosis Factor alpha, IL-1Ra)
Measured: Change of inflammatory markers during exercise stimulation at baseline compared to change of inflammatory markers during exercise stimulation at day 7
Muscle soreness
Measured: Change in muscle soreness before and after exercise stimulation at baseline compared to change in muscle soreness before and after exercise stimulation at day 7
Activity induced Fatigue (ACTIF) Scale
Measured: Change in ACTIF before and after exercise stimulation at baseline compared to change in ACTIF before and after exercise stimulation at day 7
Depression
Measured: Change in depression during exercise stimulation at baseline compared to change in depression at day 7
Change of vascular function (CAVI, pulse wave velocity, AVR)
Measured: Change in vascular function during exercise stimulation at baseline compared to change of vascular function at day 7
glucose metabolism
Measured: Change glucose metabolism during exercise stimulation at basleine compared to change in glucose metabolism during exercise stimulation at day 7
Cognition
Measured: Change in cognition during exercise stimulation at baseline compared to change in cognition at day 7
Motor strength
Measured: Change in motor strength during exercise stimulation at baseline compared to change in motor stength at day 7
Insulin
Measured: Change in insulin during exercise stimulation at baseline compared to change in insulin at day 7
Glucagon
Measured: Change in glucagon during exercise stimulation at baseline compared to change in glucagon at day 7
GLP-1
Measured: Change in GLP-1 during exercise stimulation at baseline compared to change in GLP-1 at day 7
Cortisol
Measured: Change in cortisol during exercise stimulation at baseline compared to change in cortisol at day 7
Creatinkinase
Measured: Change in creatinkinase during exercise stimulation at baseline compared to change in creatinkinase at day 7
Growth hormone
Measured: Change of growth hormone during exercise stimulation at baseline compared to change of growth hormone during exercise stimulation at day 7
Copeptin
Measured: Change of copeptin during exercise stimulation at baseline compared to change of copeptin during exercise stimulation at day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2013 (estimated)
- Study startDec 2011
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marc Y.Donath
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Marc Y.Donath, University of Zurich
- Investigators
- Marc Y Donath, MD, Principal investigator, University of Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01771445
- Sponsor's protocol ID
- MUSIL 294/10
- Acronym
- MUSIL
- Status last verified
- Jan 2014
- First submitted
- 29 Feb 2012
- Last updated
- 8 Jan 2014
- Results posted
- No
Publications
Nordmann TM, Seelig E, Timper K, Cordes M, Coslovsky M, Hanssen H, Schmidt-Trucksass A, Donath MY. Muscle-Derived IL-6 Is Not Regulated by IL-1 during Exercise. A Double Blind, Placebo-Controlled, Randomized Crossover Study. PLoS One. 2015 Oct 8;10(10):e0139662. doi: 10.1371/journal.pone.0139662. eCollection 2015.
PubMed 26448147
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Interleukin-1 in the Regulation of Muscle Derived Interleukin-6 During Exercise
- ClinicalTrials.gov ID
- NCT01771445
- Acronym / sponsor ID
- MUSIL / MUSIL 294/10
- Conditions
- Type 2 Diabetes
- Keywords
- IL-1, IL-6, Inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Marc Y.DonathUniversity, hospital or other
- Study start
- Dec 2011
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 18 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aim: Evaluate the regulation of muscle derived Interleukin-6 (IL-6)during exercise and in particular whether it is regulated by the Interleukin-1 (IL-1) system.
Rationale: It has been shown that IL-1 antagonism improves glycemia and insulin secretion in patients with type 2 Diabetes. However, IL-1 antagonism also decreases IL-6 levels. The effect if IL-6 on the glucose metabolism has been unclear in the past and subject to intense debate, with recent evidence indicating a beneficial role in regulating glucose metabolism. However little is known about regulation of muscle-induced IL-6 produced during exercise. It is therefore our aim to investigate whether exercise induced increases in IL-6 are dependent on the IL-1 system. If IL-1 antagonism does decrease IL-6 and along with it, the beneficial potential of IL-6, this may require additional medication like IL-6 substitution or dipeptidyl peptidase-IV (DPP-IV)antagonists.
In addition, the investigators will assess the effect of IL-1 antagonism on insulin and Glucagon like peptide-1 (GLP-1) secretion as well as muscle soreness,fatigue and vascular function in response to an acute exercise bout.
Detailed description
This is a randomized placebo-controlled, double blind, cross-over, proof-of-concept study.
The study will consist of one screening visit followed by 3 study visits. During the first two study visits, the subjects (20 apparently healthy, lean men) will perform a submaximal exercise bout on a treadmill for 60 minutes. Subjects will be randomly assigned into two groups consisting each of 10 subjects receiving study medication in a double-blinded, crossed over manner.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IL-1Ra | Active comparator | Drug: IL-1Ra |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- male
- non-smoking
- apparently healthy
- BMI > 18 and < 26kg/m2
- Age 20-50 years
Key exclusion criteria (15 listed)
- Clinical signs of infection in the week before inclusion or history of infection during the last 3 months (CRP > 5mg/L)
- Impaired fasting glucose (fasting plasma glucose > 5.5mmol/L)
- Hematologic disease (leukocyte count < 1.5x109/L, hemoglobin < 11 g/dL, platelets < 100 x 103/uL)
- Kidney disease (creatinine > 1.5 mg/dL for men and 1.4mg/dL for woman)
- Liver disease (transaminases > 2x upper normal range)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IL-1Ra100mg, s.c, once only | Drug | IL-1Ra |
| Placebo100mg, s.c., once only | Drug | Placebo |
Primary outcome
IL6
Time frame: Change of IL6 during exercise stimulation at baseline compared to change of IL6 during exercise stimulation at day 7
15 secondary outcomes
change of inflammatory markers (CRP, Tumor Necrosis Factor alpha, IL-1Ra)
Time frame: Change of inflammatory markers during exercise stimulation at baseline compared to change of inflammatory markers during exercise stimulation at day 7
Muscle soreness
Time frame: Change in muscle soreness before and after exercise stimulation at baseline compared to change in muscle soreness before and after exercise stimulation at day 7
Activity induced Fatigue (ACTIF) Scale
Time frame: Change in ACTIF before and after exercise stimulation at baseline compared to change in ACTIF before and after exercise stimulation at day 7
Depression
Time frame: Change in depression during exercise stimulation at baseline compared to change in depression at day 7
Change of vascular function (CAVI, pulse wave velocity, AVR)
Time frame: Change in vascular function during exercise stimulation at baseline compared to change of vascular function at day 7
glucose metabolism
Time frame: Change glucose metabolism during exercise stimulation at basleine compared to change in glucose metabolism during exercise stimulation at day 7
Cognition
Time frame: Change in cognition during exercise stimulation at baseline compared to change in cognition at day 7
Motor strength
Time frame: Change in motor strength during exercise stimulation at baseline compared to change in motor stength at day 7
Insulin
Time frame: Change in insulin during exercise stimulation at baseline compared to change in insulin at day 7
Glucagon
Time frame: Change in glucagon during exercise stimulation at baseline compared to change in glucagon at day 7
GLP-1
Time frame: Change in GLP-1 during exercise stimulation at baseline compared to change in GLP-1 at day 7
Cortisol
Time frame: Change in cortisol during exercise stimulation at baseline compared to change in cortisol at day 7
Creatinkinase
Time frame: Change in creatinkinase during exercise stimulation at baseline compared to change in creatinkinase at day 7
Growth hormone
Time frame: Change of growth hormone during exercise stimulation at baseline compared to change of growth hormone during exercise stimulation at day 7
Copeptin
Time frame: Change of copeptin during exercise stimulation at baseline compared to change of copeptin during exercise stimulation at day 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2014.
- Derived from this study: PubMed 26448147Nordmann TM, Seelig E, Timper K, Cordes M, Coslovsky M, Hanssen H, Schmidt-Trucksass A, Donath MY. Muscle-Derived IL-6 Is Not Regulated by IL-1 during Exercise. A Double Blind, Placebo-Controlled, Randomized Crossover Study. PLoS One. 2015 Oct 8;10(10):e0139662. doi: 10.1371/journal.pone.0139662. eCollection 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Y Donath, MD principal investigator
University of Basel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing IL-1Ra in people with Type 2 Diabetes, run by Marc Y.Donath at 1 site in Switzerland.
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 7 inclusion and 15 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 Jan 2014. 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 Switzerland. 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?
IL6 (time frame: Change of IL6 during exercise stimulation at baseline compared to change of IL6 during exercise stimulation at day 7). 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 NCT01771445, which also lists 1 linked publication.
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 Jan 2014.