The Effect of Anakinra on Insulin Secretion

Study Overview
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Brief Summary
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Rationale: Once diabetes develops, β-cell function progressively deteriorates and therapeutic approaches that prevent of delay loss of β-cell function are needed in the treatment of type 2 diabetes mellitus. Recent findings suggest that interleukin-1 (IL-1) may be involved in the progressive β-cell dysfunction in type 2 diabetes mellitus. Objective: to determine whether blocking IL-1β by recombinant human IL-1ra (anakinra) improves beta-cell function in subjects with β-cell dysfunction.

Official Title
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The Effect of Interleukin-1 Receptor Antagonist on Insulin Secretion in Subjects With Beta Cell Dysfunction

Conditions
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Glucose Intolerance, Impaired Insulin Secretion, Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: Anakinra


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Impaired glucose tolerance assessed by oral glucose tolerance test and/or impaired fasting glucose ( ≥ 5.6 mmol/L) and/or HbA1c levels of 5.7-6.4% BMI >25 kg/m2 Age 40-70 years Exclusion Criteria: Known diabetes mellitus Fasting plasma glucose ≥ 7.0 mmol/L or HbA1c ≥ 6.5% Immunodeficiency or immunosuppressive treatment (including TNFα blocking agents and corticosteroids) Use of anti-inflammatory drugs ( including corticosteroids and non steroidal anti-inflammatory drugs, 100 mg or less of aspirin is allowed) Signs of current infection (fever, C-reactive protein >30 mmol/L, treatment with antibiotics, previous or current diagnosis of tuberculosis) A history of recurrent infections Pregnancy or breastfeeding (contraception of at least 3 months before inclusion is required) Liver disease defined as aspartate aminotransferase or alanine aminotransferase level of more than three times the upper limit of normal range Renal disease defined as MDRD < 60 ml/min/1.73m2 Neutropenia < 2x 109/L Inability to understand the nature and extent of the trial and the procedures required. Any medical condition that might interfere with the current study protocol Participation in a drug trial within 60 days prior to the first dose

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anakinra<br>Anakinra 150 mg/day during four weeks | Drug: Anakinra<br>* 150 mg sc once daily during four weeks<br>* Other names: Interleukin1-receptor antagonist;|
| Placebo Comparator: Placebo<br>Placebo during four weeks | Drug: Anakinra<br>* 150 mg sc once daily during four weeks<br>* Other names: Interleukin1-receptor antagonist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effect of anakinra on insulin secretion, as derived from hyperglycemic clamps . |  | after 4 weeks of treatment with anakinra | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effect on anakinra on insulin sensitivity. | Oral glucose tolerance test | after 4 week treatment of anakinra | 
| Effects of anakinra on fat cell morphology and gene expression | Fatbiopsy | after 4 weeks of treatment with anakinra |