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

Marc Y.Donath

Status

Completed

Conditions

Type 2 Diabetes

Treatments

Drug: Placebo

Drug: IL-1Ra

Study type

Interventional

Funder types

Other

Identifiers

NCT01771445

MUSIL 294/10

Details and patient eligibility

About

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.

Full 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.

Enrollment

18 patients

Sex

Male

Ages

20 to 50 years old

Volunteers

Accepts Healthy Volunteers

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