Interleukin-1 Receptor Antagonist and Insulin Sensitivity

December 16, 2010 updated by: Radboud University Medical Center

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Nijmegen, Netherlands, 6500 HB
        • Rabdoud University Nijmegen Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo during four weeks
Drug: Placebo
placebo s/c daily for four weeks
Experimental: Anakinra group
Anakinra 150 mg/day during four weeks
Drug: Anakinra (Kineret)
anakinra 150 mg s/c. daily for four weeks
Other Names:
  • kineret

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
after four weeks of treatment

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Investigators

  • Study Chair: C J Tack, Prof Dr, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Anticipated)

March 1, 2010

Study Completion (Anticipated)

July 1, 2010

Study Registration Dates

First Submitted

June 25, 2009

First Submitted That Met QC Criteria

June 25, 2009

First Posted (Estimate)

June 26, 2009

Study Record Updates

Last Update Posted (Estimate)

December 17, 2010

Last Update Submitted That Met QC Criteria

December 16, 2010

Last Verified

June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCN001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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