Hyperinsulinemia in Prediabetes Mediated by Interleukin-1β (Hyper-PreDIL)

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

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.

Study Overview

• Status: Recruiting
• Conditions: PreDiabetes; Hyperinsulinemia
• Intervention / Treatment: Drug: Anakinra; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marc Donath, Prof.; Phone Number: +41 61 265 25 25; Email: marc.donath@usb.ch
• Study Contact Backup: Name: Matthias Hepprich, MD; Phone Number: +41 61 265 25 25; Email: matthias.hepprich@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Matthias Hepprich, MD; Phone Number: +41 61 265 25 25; Email: matthias.hepprich@usb.ch
    • Contact: Marc Donath, Prof.; Phone Number: +41 61 265 50 78; Email: marc.donath@usb.ch
    • Principal Investigator: Marc Donath, MD
    • Sub-Investigator: Matthias Hepprich, MD
    • Sub-Investigator: Justus Fischer, MD
    • Sub-Investigator: Stefanie Dobler, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Intervention; Patients receive investigational product	Drug: Anakinra; 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
Placebo Comparator: Control Intervention; Patients receive placebo	Drug: Placebo; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Marc Donath, Prof., University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2023
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 11, 2023

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: anakinra (Kineret®)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance; Hyperinsulinism; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: 2023-00497; kt23Donath2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No