IL-1-receptor Antagonist During Cephalic Phase of Insulin Secretion in Health and Type 2 Diabetes

NCT04227769 | Terminated Phase 2 DMC

• 1 other identifier: EKNZ 2019-02307
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective, randomized, mixed double- and single-blinded, placebo-controlled, cross-over clinical trial to test whether acute treatment with an IL-1 receptor antagonist impacts insulin secretion over time during the cephalic phase, defined as the first 10 minutes after the first sensorial contact to food, in healthy individuals in healthy humans (Group 1) and in obese patients with type 2 diabetes (Group 2).

Conditions

Diabetes Mellitus Type 2 in Obese; Inflammation; Metabolic Disease; Glucose Metabolism Disorders (Including Diabetes Mellitus)

Keywords

anakinra; cephalic phase of insulin secretion

Outcome Measures

Primary Outcomes (2)

• Change in insulin concentration in blood during the cephalic phase of insulin secretion in healthy individuals

  Insulin concentration in blood at 0, 3,6 and 10 minutes after ingestion of a standardized meal in healthy individuals.

  10 minutes

• Change in insulin concentration in blood during the cephalic phase of insulin secretion in obese patients with type 2 diabetes

  Insulin concentration in blood at 0, 3, 6 and 10 minutes after ingestion of a standardized meal in healthy individuals in obese patients with type 2 diabetes.

  10 minutes

Secondary Outcomes (12)

• Change of C-peptide

  6 hours

• Change of insulin

  6 hours

• Change of glucose

  6 hours

• Change of glucagon

  6 hours

• Change of GLP-1

  6 hours

Study Arms (2)

healthy individuals

EXPERIMENTAL

Two crossover visits with a washout period of at least 4 days in-between visits and at most two weeks: A) subcutaneous saline injection 3h before an oral standardized meal, B) subcutaneous injection of 100 mg of the IL-1 receptor antagonist anakinra 3h before an oral standardized meal. Treatments will be placebo controlled, crossover, double blinded. Standard dose of Anakinra (Kineret®; r-metHuIL-1ra, Swedish Orphan Biovitrum AB), i. e. 100 mg/ 0.67 ml s. c. or 0.67 ml of saline s. c. (placebo)

Drug: Anakinra Prefilled Syringe

obese patients with type 2 diabetes

EXPERIMENTAL

Three crossover visits with a washout period of at least 4 days in-between: A) subcutaneous saline injection 3h before an oral standardized meal, B) subcutaneous injection of 100 mg of the IL-1 receptor antagonist anakinra 3h before an oral standardized meal, C) Additionally, after the second study day, participant in group 2 will be trained to self-inject the medication for 6 days. On the 7th day, an oral standardized meal test will be performed. Standard dose of Anakinra (Kineret®; r-metHuIL-1ra, Swedish Orphan Biovitrum AB), i. e. 100 mg/ 0.67 ml s. c. or 0.67 ml of saline s. c. (placebo)

Drug: Anakinra Prefilled Syringe

Interventions

Anakinra Prefilled Syringe DRUG

Subcutaneous injection of 100 mg/ 0.67 ml of Kineret or placebo

Also known as: Kineret

healthy individuals; obese patients with type 2 diabetes

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and ≤ 70 years at screening
• Male or female of non-child-bearing potential (meaning for women: not currently pregnant, post-menopausal female or using condoms and either intrauterine devices or 3-monthly contraceptive injection or birth-control pill.)
• Healthy subjects:
• No apparent disease requiring medication
• BMI \< 25 kg/ m2
• C-reactive protein ≤ 2 mg/L
• Obese diabetic type 2 subjects:
• Type 2 diabetes
• HbA1c 7.0 -10.0%
• BMI ≥ 30.0 kg/m2
• C-reactive protein ≥ 2 mg/L

You may not qualify if:

• Subjects will be excluded from the study if they meet any of the following criteria:
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation
• Aversion or allergy to paracetamol or any component of the meal.
• Known history of allergy or hypersensitivity to any component of the investigational product formulations
• Concomitant treatment with GLP-1 agonists, DPP-4 inhibitors, insulin or insulin derivative
• Change in diabetes medication within the last 30 days
• Any biologic drugs targeting the immune system
• Fever, or other signs of infection requiring antibiotics within 3 weeks prior to screening, history of recurrent infection, immunodeficiency, known HIV or tuberculosis infection, active foot ulcer
• Participation in another study with investigational drug within 30 days prior to Screening and during the present study
• eGFR \< 30 mL/min/1.73m2 per MDRD formula or kidney transplant (regardless of renal function)
• Known active or recurrent hepatic disorder (including cirrhosis, hepatitis B and hepatitis C, or confirmed ALAT/ASAT levels \> 3 times ULN or total bilirubin \> 2 times ULN),
• Haemoglobin \<10.0 g/dL, white blood cell \<3.0 x 103/mm3, platelet count \<125 x 103/mm3
• Atrial fibrillation and/or a pacemaker

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, Basel BS, 4031, Switzerland

Location

MeSH Terms

Conditions

Inflammation; Metabolic Diseases; Glucose Metabolism Disorders

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Marc Y Donath, Prof. Dr. MD

  University of Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomized, double-blinded and open-label, placebo-controlled, partly cross-over clinical trial
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: January 14, 2020
• Study Start: January 13, 2020
• Primary Completion: May 28, 2024
• Study Completion: May 28, 2024
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)