Interleukin-1 Receptor Antagonist and Insulin Sensitivity
Recruitment status was Active, not recruiting
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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 |
- 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 ]
- 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 |
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 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 May 22, 2013