Overview

This trial is active, not recruiting.

Conditions diabetes mellitus, type 2, insulin resistance
Treatments anakinra (kineret), placebo
Phase phase 2
Sponsor Radboud University
Start date June 2009
End date March 2010
Trial size 12 participants
Trial identifier NCT00928876, UMCN001

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Anakinra 150 mg/day during four weeks
anakinra (kineret) kineret
anakinra 150 mg s/c. daily for four weeks
(Placebo Comparator)
Placebo during four weeks
placebo
placebo s/c daily for four weeks

Primary Outcomes

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

Secondary Outcomes

Measure
pancreatic beta cell function als tested by oral glucose tolerance test, pro-insulin/insulin ratio
time frame: after four weeks of treatment
lipid profile
time frame: after four weeks of treatment
systemic inflammation
time frame: after four weeks of treatment

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Obese, Insulin Resistant Individuals
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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2010.
Information provided to ClinicalTrials.gov by Radboud University.