Hyperinsulinemia, PreDiabetes
Conditions
Keywords
anakinra (Kineret®)
Brief summary
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.
Interventions
DRUGAnakinra
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
DRUGPlacebo
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
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Placebo controlled, double-blind, randomized, cross-over proof-of-concept study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in insulin concentration following a standardized mixed-meal test | two time assessment at baseline and after 1-2 weeks | 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. |
| Change in glucose concentration following a standardized mixed-meal test | two time assessment at baseline and after 1-2 weeks | 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. |
| Change in c-peptide concentration following a standardized mixed-meal test | two time assessment at baseline and after 1-2 weeks | 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. |
| Change in insulinogenic index (IGI) concentration following a standardized mixed-meal test | two time assessment at baseline and after 1-2 weeks | 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. |
Countries
Switzerland
Outcome results
None listed