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

NCT ID: NCT01771445

Last Updated: 2014-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2013-10-31

Brief 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. 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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

IL-1Ra

Group Type: ACTIVE_COMPARATOR

IL-1Ra

Intervention Type: DRUG

100mg, s.c, once only

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

100mg, s.c., once only

Interventions

IL-1Ra

100mg, s.c, once only

Intervention Type: DRUG

Placebo

100mg, s.c., once only

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Marc Y.Donath

OTHER

Sponsor Role: lead

Responsible Party

Marc Y.Donath

Prof.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marc Y Donath, MD

Role: PRINCIPAL_INVESTIGATOR

University of Basel

Locations

University Hospital of Basel, Division of Endocrinology

Basel, Basel, Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 26448147 (View on PubMed)

Other Identifiers

MUSIL 294/10

Identifier Type: -

Identifier Source: org_study_id