Interleukin-1 Receptor Antagonist and Insulin Sensitivity

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by Radboud University.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00928876
First received: June 25, 2009
Last updated: December 16, 2010
Last verified: June 2009
  Purpose

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 Intervention Phase
Diabetes Mellitus, Type 2
Insulin Resistance
Drug: Anakinra (Kineret)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Obese, Insulin Resistant Individuals

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • pancreatic beta cell function als tested by oral glucose tolerance test, pro-insulin/insulin ratio [ Time Frame: after four weeks of treatment ] [ Designated as safety issue: No ]
  • lipid profile [ Time Frame: after four weeks of treatment ] [ Designated as safety issue: No ]
  • systemic inflammation [ Time Frame: after four weeks of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: June 2009
Estimated Study Completion Date: July 2010
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Placebo
placebo s/c daily for four weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00928876

Locations
Netherlands
Rabdoud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Investigators
Study Chair: C J Tack, Prof Dr Radboud University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Dr. C.J. Tack, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov Identifier: NCT00928876     History of Changes
Other Study ID Numbers: UMCN001
Study First Received: June 25, 2009
Last Updated: December 16, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
anakinra
Diabetes mellitus, type 2
Insulin resistance
Interleukin-1beta

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
Insulin
Interleukin 1 Receptor Antagonist Protein
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014