Hyper-PreDIL: Hyperinsulinemia in Prediabetes Mediated by Interleukin-1β

• Sponsor: University Hospital, Basel, Switzerland (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05854251
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 12
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperinsulinemia; PreDiabetes	Drug: Anakinra; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Placebo controlled, double-blind, randomized, cross-over proof-of-concept studyPlacebo controlled, double-blind, randomized, cross-over proof-of-concept study
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Hyperinsulinemia in Prediabetes Mediated by Interleukin-1β- The Hyper-PreDIL-Study
• Anticipated Study Start Date: May 1, 2023
• Anticipated Primary Completion Date: May 1, 2024
• Anticipated Study Completion Date: May 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Basel	Basel		Switzerland	4031

Sponsors and Collaborators

• University Hospital, Basel, Switzerland

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT05854251
• Other Study ID Numbers: kt23Donath2, 2023-00497
• First Posted: May 11, 2023
• Last Update Posted: May 11, 2023
• Last Verified: May 1, 2023

• 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
• Keywords provided by University Hospital, Basel, Switzerland: anakinra (Kineret®)
• Additional relevant MeSH terms: Prediabetic State; Glucose Intolerance; Hyperinsulinism; Interleukin 1 Receptor Antagonist Protein

Study Results

No Results Posted as of May 11, 2023