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.|
|ClinicalTrials.gov 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
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|
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|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
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
placebo s/c daily for four weeks
- 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 ]
- 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 ]
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 ClinicalTrials.gov identifier (NCT number): NCT00928876
|Rabdoud University Nijmegen Medical Centre|
|Nijmegen, Netherlands, 6500 HB|
|Study Chair:||C J Tack, Prof Dr||Radboud University|