Interleukin-1 Receptor Antagonist and Insulin Sensitivity

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by Radboud University.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00928876
First received: June 25, 2009
Last updated: December 16, 2010
Last verified: June 2009

June 25, 2009
December 16, 2010
June 2009
March 2010   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00928876 on ClinicalTrials.gov Archive Site
  • pancreatic beta cell function als tested by oral glucose tolerance test, pro-insulin/insulin ratio [ Time Frame: after four weeks of treatment ] [ Designated as safety issue: No ]
  • lipid profile [ Time Frame: after four weeks of treatment ] [ Designated as safety issue: No ]
  • systemic inflammation [ Time Frame: after four weeks of treatment ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Interleukin-1 Receptor Antagonist and Insulin Sensitivity
Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Obese, Insulin Resistant Individuals

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Diabetes Mellitus, Type 2
  • Insulin Resistance
  • Drug: Anakinra (Kineret)
    anakinra 150 mg s/c. daily for four weeks
    Other Name: kineret
  • Drug: Placebo
    placebo s/c daily for four weeks
  • Experimental: Anakinra group
    Anakinra 150 mg/day during four weeks
    Intervention: Drug: Anakinra (Kineret)
  • Placebo Comparator: Placebo
    Placebo during four weeks
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
12
July 2010
March 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00928876
UMCN001
No
Prof. Dr. C.J. Tack, Radboud University Nijmegen Medical Centre
Radboud University
Not Provided
Study Chair: C J Tack, Prof Dr Radboud University
Radboud University
June 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP