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

Type 2 Diabetes Clinical Trial

— MUSIL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01771445
• Other study ID #: MUSIL 294/10
• Status: Completed
• Phase: N/A
• First received: February 29, 2012
• Last updated: January 7, 2014
• Start date: December 2011
• Est. completion date: October 2013

Study information

• Verified date: January 2014
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Type 2 Diabetes

Intervention

Drug:
• IL-1Ra
100mg, s.c, once only
• Placebo
100mg, s.c., once only

Locations

Country	Name	City	State
Switzerland	University Hospital of Basel, Division of Endocrinology	Basel

Sponsors (1)

Lead Sponsor	Collaborator
Marc Y.Donath

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IL6		Change of IL6 during exercise stimulation at baseline compared to change of IL6 during exercise stimulation at day 7	No
Secondary	change of inflammatory markers (CRP, Tumor Necrosis Factor alpha, IL-1Ra)		Change of inflammatory markers during exercise stimulation at baseline compared to change of inflammatory markers during exercise stimulation at day 7	No
Secondary	Muscle soreness		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	No
Secondary	Activity induced Fatigue (ACTIF) Scale		Change in ACTIF before and after exercise stimulation at baseline compared to change in ACTIF before and after exercise stimulation at day 7	No
Secondary	Depression		Change in depression during exercise stimulation at baseline compared to change in depression at day 7	No
Secondary	Change of vascular function (CAVI, pulse wave velocity, AVR)		Change in vascular function during exercise stimulation at baseline compared to change of vascular function at day 7	No
Secondary	glucose metabolism		Change glucose metabolism during exercise stimulation at basleine compared to change in glucose metabolism during exercise stimulation at day 7	No
Secondary	Cognition		Change in cognition during exercise stimulation at baseline compared to change in cognition at day 7	No
Secondary	Motor strength		Change in motor strength during exercise stimulation at baseline compared to change in motor stength at day 7	No
Secondary	Insulin		Change in insulin during exercise stimulation at baseline compared to change in insulin at day 7	No
Secondary	Glucagon		Change in glucagon during exercise stimulation at baseline compared to change in glucagon at day 7	No
Secondary	GLP-1		Change in GLP-1 during exercise stimulation at baseline compared to change in GLP-1 at day 7	No
Secondary	Cortisol		Change in cortisol during exercise stimulation at baseline compared to change in cortisol at day 7	No
Secondary	Creatinkinase		Change in creatinkinase during exercise stimulation at baseline compared to change in creatinkinase at day 7	No
Secondary	Growth hormone		Change of growth hormone during exercise stimulation at baseline compared to change of growth hormone during exercise stimulation at day 7	No
Secondary	Copeptin		Change of copeptin during exercise stimulation at baseline compared to change of copeptin during exercise stimulation at day 7	No