Hyperinsulinemia in Prediabetes Mediated by Interleukin-1β

Study Overview
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Brief Summary
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The goal of this clinical study is to test whether postprandial insulin secretion in subjects with prediabetes is mediated by Interleukin-1β and may be influenced by administration of the medicinal product anakinra (Kineret®). The main question it aims to answer is whether there is a difference in insulin secretion following a standardized mixed-meal test under anakinra compared to placebo.

Official Title
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Hyperinsulinemia in Prediabetes Mediated by Interleukin-1β- The Hyper-PreDIL-Study

Conditions
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Hyperinsulinemia, PreDiabetes

Intervention / Treatment
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* Drug: Anakinra
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with prediabetes defined by HbA1c 5.7-6.4 % or fasting plasma glucose 6.1-6.9 mmol/l or plasma glucose 2 h following 75g glucose ingestion of 7.8-11.0 mmol/l. BMI ≥ 28 kg/m2 Age ≥ 18 years C-reactive protein ≥ 2 mg/dl For subjects with reproductive potential, willingness to use contraceptive measures adequate to prevent the subject from becoming pregnant during the study Exclusion Criteria: Upper gastrointestinal surgery Diagnosis of any type of diabetes mellitus Signs of current infection Use of any glucose lowering medication within the last three months Use of investigational drug up to one week prior to start of treatment phase. Anti-inflammatory medication, including systemic glucocorticoid therapy. Neutropenia (leukocyte count < 1.5 × 109/L or absolute neutrophil count (ANC) < 0.5 × 109/L) Anemia (hemoglobin < 11 g/dL for males, < 10 g/dL for females) Clinically significant kidney or liver disease (creatinine > 1.5 mg/dL, aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) > 2 × ULN, alkaline phosphatase > 2 × ULN, or total bilirubin [tBili] > 1.5 × ULN) Uncontrolled disease Currently pregnant or breastfeeding No subjects meeting the criteria for vulnerability. Participation in another study with investigational drug within the 30 days preceding and during the present study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo controlled, double-blind, randomized, cross-over proof-of-concept study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Intervention<br>Patients receive investigational product | Drug: Anakinra<br>* Subjects receive an s.c. injection of 100 mg Anakinra on the evening before and on the respective study day 60 minutes before ingestion of the mixed-meal<br>|
| Placebo Comparator: Control Intervention<br>Patients receive placebo | Drug: Placebo<br>* 0.67 ml of s.c. injection of saline will be taken on the evening before and on the respective study day 60 minutes before ingestion of the mixed-meal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin concentration following a standardized mixed-meal test | Changes in insulin concentration (mmol/l) under anakinra compared to placebo. Blood will be analysed 90 and 0 min before and 30 min, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs after the mixed meal. | two time assessment at baseline and after 1-2 weeks | 
| Change in glucose concentration following a standardized mixed-meal test | Changes in glucose concentration (mmol/l) under anakinra compared to placebo. Blood will be analysed 90 and 0 min before and 30 min, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs after the mixed meal. | two time assessment at baseline and after 1-2 weeks | 
| Change in c-peptide concentration following a standardized mixed-meal test | Changes in c-peptide concentration (nmol/l) under anakinra compared to placebo. Blood will be analysed 90 and 0 min before and 30 min, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs after the mixed meal. | two time assessment at baseline and after 1-2 weeks | 
| Change in insulinogenic index (IGI) concentration following a standardized mixed-meal test | Changes in insulinogenic index (IGI) (I30 - I0)/(G30 - G0) under anakinra compared to placebo. Blood will be analysed 90 and 0 min before and 30 min, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs after the mixed meal. | two time assessment at baseline and after 1-2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anakinra (Kineret®)