Interleukin-1 Receptor Antagonist and Insulin Sensitivity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00928876
Recruitment Status : Unknown
Verified June 2009 by Radboud University.
Recruitment status was:  Active, not recruiting
First Posted : June 26, 2009
Last Update Posted : December 17, 2010
Information provided by:
Radboud University

Brief Summary:

Obesity is characterized by continuous low-grade inflammation. This is an important link between obesity and insulin resistance.

Results from the investigators' own group of in vitro and in vivo research on mice show that Interleukin-1 is involved in the process of developing insulin resistance. Earlier it has been shown that interleukin-1 receptor antagonist in human subjects improves glycemic control. The investigators' hypothesis is that this is due to improved insulin sensitivity.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Insulin Resistance Drug: Anakinra (Kineret) Drug: Placebo Phase 2

Detailed Description:

The prevalence of obesity is increasing fast. Obesity is one of the most common acquired risk factors for insulin resistance. As a consequence the prevalence of type 2 diabetes mellitus is rising fast as well.

Interleukin 6 and Tumor Necrosis Factor alfa are well known pro-inflammatory cytokines that have been linked to insulin resistance. Results from our own group show that interleukin-1 is also involved in the process of developing insulin resistance.

Earlier research projects studied the effect of Interleukin-1 receptor antagonist (Anakinra) on glycemic control in subjects with type 2 diabetes mellitus. It was shown that glycemic control was improved. The authors conclude that this is the result of improved function of pancreatic beta cells.

These results are in contrast to our results of in vitro en in vivo research on mice, which show improved insulin sensitivity by Interleukin-1 receptor antagonist.

A possible explanation for not finding an effect on insulin sensitivity by earlier research projects may be that it is difficult to reliable quantify insulin sensitivity in this group of patients with concurrent changes in glycemic control, extensive co-morbidity and medication use, who might be at the rather extreme end of insulin resistance. Furthermore a relatively low dose of Anakinra was used.

Altogether we hypothesize that the effect of Interleukin-1 is not only mediated through better pancreatic beta-cell function, but that Interleukin-1 blocking by recombinant Interleukin-1 receptor antagonist will also diminish insulin resistance.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Obese, Insulin Resistant Individuals
Study Start Date : June 2009
Estimated Primary Completion Date : March 2010
Estimated Study Completion Date : July 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Anakinra group
Anakinra 150 mg/day during four weeks
Drug: Anakinra (Kineret)
anakinra 150 mg s/c. daily for four weeks
Other Name: kineret
Placebo Comparator: Placebo
Placebo during four weeks
Drug: Placebo
placebo s/c daily for four weeks

Primary Outcome Measures :
  1. to determine the effect of Interleukin-1 receptor antagonist on insulin sensitivity, as derived from glucose infusion rate measured by euglycemic hyperinsulinemic clamp [ Time Frame: after four weeks of treatment ]

Secondary Outcome Measures :
  1. pancreatic beta cell function als tested by oral glucose tolerance test, pro-insulin/insulin ratio [ Time Frame: after four weeks of treatment ]
  2. lipid profile [ Time Frame: after four weeks of treatment ]
  3. systemic inflammation [ Time Frame: after four weeks of treatment ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • adult subjects with a BMI > 30 kg/m2
  • 3 or more characteristics of the metabolic syndrome

Exclusion Criteria:

  • inability to give informed consent
  • age < 18 years
  • known diabetes mellitus
  • fasting plasma glucose > 7,0 mmol/l or HbA1c > 6,2%
  • presence of any medical condition that might interfere with the current study protocol
  • immunodeficiency of immunosuppressive treatment
  • anti-inflammatory drugs (100 mg of aspirin/day is allowed)
  • signs of current infection
  • history of recurrent infections
  • pregnancy or breast feeding
  • liver disease
  • renal disease
  • neutropenia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00928876

Rabdoud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Study Chair: C J Tack, Prof Dr Radboud University

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Prof. Dr. C.J. Tack, Radboud University Nijmegen Medical Centre Identifier: NCT00928876     History of Changes
Other Study ID Numbers: UMCN001
First Posted: June 26, 2009    Key Record Dates
Last Update Posted: December 17, 2010
Last Verified: June 2009

Keywords provided by Radboud University:
Diabetes mellitus, type 2
Insulin resistance

Additional relevant MeSH terms:
Diabetes Mellitus
Insulin Resistance
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Interleukin 1 Receptor Antagonist Protein
Hypoglycemic Agents
Physiological Effects of Drugs
Antirheumatic Agents