Interleukin-1 Receptor Antagonist and Insulin Sensitivity

Radboud University Medical Center

Status and phase: Unknown; Phase 2

Conditions: Insulin Resistance; Diabetes Mellitus, Type 2

Treatments: Drug: Placebo; Drug: Anakinra (Kineret)

Study type: Interventional

Funder types: Other

Identifiers

NCT00928876

UMCN001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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12 participants in 2 patient groups, including a placebo group

Anakinra group

Experimental group

Description:

Anakinra 150 mg/day during four weeks

Treatment:

Drug: Anakinra (Kineret)

Placebo

Placebo Comparator group

Description:

Placebo during four weeks

Treatment:

Drug: Placebo