Hyperinsulinemia in Prediabetes Mediated by Interleukin-1β

NCT05854251 | Completed Phase 2

• 1 other identifier: 2023-00497; kt23Donath2
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperinsulinemia; PreDiabetes

Keywords

anakinra (Kineret®)

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (2)

Experimental Intervention

EXPERIMENTAL

Patients receive investigational product

Drug: Anakinra

Control Intervention

PLACEBO COMPARATOR

Patients receive placebo

Drug: Placebo

Interventions

Anakinra DRUG

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

Experimental Intervention

Placebo DRUG

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

Control Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

Location

MeSH Terms

Conditions

Hyperinsulinism; Prediabetic State

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Marc Donath, Prof.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Placebo controlled, double-blind, randomized, cross-over proof-of-concept study

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: May 11, 2023
• Study Start: June 15, 2023
• Primary Completion: May 17, 2024
• Study Completion: May 17, 2024
• Last Updated: January 29, 2025

Record last verified: 2025-01

Locations

CH (1)