Our primary objective is to determine whether blocking of IL-1 by recombinant human IL-1ra (anakinra) in insulin resistant patients improves insulin sensitivity. Secondary objectives are to determine the effect of IL-1 blockade on pancreatic beta-…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
insulin sensitivity after 4 weeks treatment with anakinra compared with
placebo.
Secondary outcome
pancreatic beta-cell function
fat cell morfology
Insulin sensitivity of fat cells
glucose control (fasting glucose, HbA1c)
concentration of hormonal (leptin, adiponectin, insulin, glucagon) and
inflammatory factors (Interleukin 1, 6, 18, hsCRP) and lipid profile
Background summary
The prevalence of obesity is increasing fast. Obesity is one of the most common
acquired riscfactors for insulin resistance. As a consequence the prevalence of
diabetes mellitus is rising fast as well.
Obese individuals are in a state of continuous low-grade inflammation.
Inflammation is an important link between obesity and insulin resistance. The
best known pro-inflammatory cytokines that have been linked to insulin
resistance are interleukin 6 and tumor necrosis factor alfa.
Results from our own group show that interleukin-1 is also involved in the
proces of developing insuline resistance.
Larsen et al conducted a study on the effect of interleukin-1 receptor
antagonist on type 2 diabetes mellitus. He shows an improved glycemic control,
which is suggested to be the result of a better function of insulin producing
pancreatic beta cells. This latest concusion is in contrast with our results by
in vitro en in vivo research on mice, which show improved insulin sensitivty by
blocking interleukin-1.
Study objective
Our primary objective is to determine whether blocking of IL-1 by recombinant
human IL-1ra (anakinra) in insulin resistant patients improves insulin
sensitivity.
Secondary objectives are to determine the effect of IL-1 blockade on pancreatic
beta-cell function, fat cell morphology and insulin sensitivity, circulating
hormonal and inflammatory factors and lipid profile.
Study design
Double blind, placebo controlled cross-over trial
Intervention
150 mg of anakinra once daily by a subcutaneous injection during 4 weeks.
Study burden and risks
Recombinant human interleukin-1 receptor antagonist (anakinra) has been
approved by the EMEA for the treatment of rheumatoid arthritis.
The risc of side effect of anakinra is relatively low. The most important side
effects are increased risc of infection, neutropenia and local injection-side
reactions. The last side effect is frequently occuring, but in 95% of the cases
it is a mild to moderate reaction, which deminishes after prolonged usage.
The dose of anankinra as used in this study is higher than the normal dose.
However this dose is used in all the studies necessary for regisration of
anakinra. An even higher dose (2mg/kg/hour) is used for the treatment of
patients with sepsis in the intensive care unit. In this studies the higher
dose of anakinra did not cause other side effects as with the usual dose of 100
mg/day.
Adverse events caused by the diagnostic procedures used in this study are
infrequent.
Postbus 9101
6500 HB Nijmegen
NL
Postbus 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
body mass index > 30 kg/m2
3 or more characteristics of the metabolic syndrome
Exclusion criteria
elevated risk for infections
pregnancy or breast-feeding
liver or renal disease
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-008603-18-NL |
| CCMO | NL26368.091.09 |