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Role of Interleukin-1 in the Regulation of Muscle Derived Interleukin-6 During Exercise (MUSIL)

This study is currently recruiting participants.
Verified January 2013 by University of Zurich
Sponsor:
Information provided by (Responsible Party):
Marc Y.Donath, University of Zurich
ClinicalTrials.gov Identifier:
NCT01771445
First received: February 29, 2012
Last updated: January 18, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention
Type 2 Diabetes
 Drug: IL-1Ra
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Role of Interleukin-1 in the Regulation of Muscle Derived Interleukin-6 During Exercise

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • IL6 [ Time Frame: Change of IL6 during exercise stimulation at baseline compared to change of IL6 during exercise stimulation at day 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Depression [ Time Frame: Change in depression during exercise stimulation at baseline compared to change in depression at day 7 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • glucose metabolism [ Time Frame: Change glucose metabolism during exercise stimulation at basleine compared to change in glucose metabolism during exercise stimulation at day 7 ] [ Designated as safety issue: No ]
  • Cognition [ Time Frame: Change in cognition during exercise stimulation at baseline compared to change in cognition at day 7 ] [ Designated as safety issue: No ]
  • Motor strength [ Time Frame: Change in motor strength during exercise stimulation at baseline compared to change in motor stength at day 7 ] [ Designated as safety issue: No ]
  • Insulin [ Time Frame: Change in insulin during exercise stimulation at baseline compared to change in insulin at day 7 ] [ Designated as safety issue: No ]
  • Glucagon [ Time Frame: Change in glucagon during exercise stimulation at baseline compared to change in glucagon at day 7 ] [ Designated as safety issue: No ]
  • GLP-1 [ Time Frame: Change in GLP-1 during exercise stimulation at baseline compared to change in GLP-1 at day 7 ] [ Designated as safety issue: No ]
  • Cortisol [ Time Frame: Change in cortisol during exercise stimulation at baseline compared to change in cortisol at day 7 ] [ Designated as safety issue: No ]
  • Creatinkinase [ Time Frame: Change in creatinkinase during exercise stimulation at baseline compared to change in creatinkinase at day 7 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Copeptin [ Time Frame: Change of copeptin during exercise stimulation at baseline compared to change of copeptin during exercise stimulation at day 7 ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: December 2011
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IL-1Ra Drug: IL-1Ra
100mg, s.c, once only
Placebo Comparator: Placebo Drug: Placebo
100mg, s.c., once only

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.

  Eligibility

Ages Eligible for Study:   20 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01771445

Contacts
Contact: Eleonora Seelig, MD 079 843 32 23 ext 0041
Contact: Katharina Timper, MD 079 843 32 23 ext 0041

Locations
Switzerland
University Hospital of Basel, Division of Endocrinology Recruiting
Basel, Switzerland
Contact: Eleonora Seelig, MD     079 843 32 23 ext 0041        
Sponsors and Collaborators
Marc Y.Donath
Investigators
Principal Investigator: Marc Y Donath, MD University of Basel
  More Information

No publications provided

Responsible Party: Marc Y.Donath, Prof., University of Zurich
ClinicalTrials.gov Identifier: NCT01771445     History of Changes
Other Study ID Numbers: MUSIL 294/10
Study First Received: February 29, 2012
Last Updated: January 18, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University of Zurich:
IL-1
IL-6
Inflammation

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
 Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013