Interleukin-1 Receptor Antagonist and Insulin Sensitivity

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Obese, Insulin Resistant Individuals

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT00928876
• Other study ID #: UMCN001
• Status: Unknown status
• Phase: Phase 2
• First received: June 25, 2009
• Last updated: December 16, 2010
• Start date: June 2009
• Est. completion date: July 2010

Study information

• Verified date: June 2009
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 12
• Est. completion date: July 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Insulin Resistance

Intervention

Drug:
• Anakinra (Kineret)
anakinra 150 mg s/c. daily for four weeks
• Placebo
placebo s/c daily for four weeks

Locations

Country	Name	City	State
Netherlands	Rabdoud University Nijmegen Medical Centre	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Larsen CM, Faulenbach M, Vaag A, Vølund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007 Apr 12;356(15):1517-26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	to determine the effect of Interleukin-1 receptor antagonist on insulin sensitivity, as derived from glucose infusion rate measured by euglycemic hyperinsulinemic clamp		after four weeks of treatment
Secondary	pancreatic beta cell function als tested by oral glucose tolerance test, pro-insulin/insulin ratio		after four weeks of treatment
Secondary	lipid profile		after four weeks of treatment
Secondary	systemic inflammation		after four weeks of treatment