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

NCT01771445 | Completed

• 1 other identifier: MUSIL 294/10
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes

Keywords

IL-1; IL-6; Inflammation

Outcome Measures

Primary Outcomes (1)

• IL6

  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)

  Change of inflammatory markers during exercise stimulation at baseline compared to change of inflammatory markers during exercise stimulation at day 7

• 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

• 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

• Depression

  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)

  Change in vascular function during exercise stimulation at baseline compared to change of vascular function at day 7

Study Arms (2)

IL-1Ra

ACTIVE COMPARATOR

Drug: IL-1Ra

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

IL-1Ra DRUG

100mg, s.c, once only

IL-1Ra

Placebo DRUG

100mg, s.c., once only

Placebo

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Marc Y.Donath: lead

Study Sites (1)

University Hospital of Basel, Division of Endocrinology

Basel, Basel, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 26448147 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Inflammation

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Marc Y Donath, MD

  University of Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: January 18, 2013
• Study Start: December 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: January 8, 2014

Record last verified: 2014-01

Locations

CH (1)