Diabetes Mellitus Type 2 in ObesePhase 2CephaliraNCT04227769
IL-1-receptor Antagonist During Cephalic Phase of Insulin Secretion in Health and Type 2 Diabetes
A Phase 2 study testing Anakinra Prefilled Syringe in people with Diabetes Mellitus Type 2 in Obese and Inflammation, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus Type 2 in Obese, Inflammation, Metabolic Disease
- What is being tested?
- Anakinra Prefilled Syringe
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteSwitzerland
- Study dates
- 13 Jan 2020to 28 May 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Main inclusion criteria:
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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).
Read the detailed description
The role of the immune system in metabolism has been extensively investigated in pancreatic islets and insulin sensitive tissues. However little attention has been given to a potential role of the innate immune system in the cephalic phase of insulin secretion. In humans, the cephalic phase of insulin secretion appear reduced in obesity and in patients with type 2 diabetes.
In this prospective, randomized, mixed double- and single-blinded, placebo-controlled, cross-over clinical trial we aim 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).
Group 1: After screening, subjects will be randomized to 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. The study will be performed in a population of healthy individuals.
Group 2: Same as for Group 1 with the following addition: 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.
Healthy subjects from group 1 will be matched for sex and age to the diabetic cohort from group 2.
- Conditions
- Diabetes Mellitus Type 2 in Obese, Inflammation, Metabolic Disease, Glucose Metabolism Disorders (Including Diabetes Mellitus)
- Being tested
- Anakinra Prefilled Syringe
- Keywords
- anakinra, cephalic phase of insulin secretion
- Medical subject headings
- Inflammation, Metabolic Diseases, Glucose Metabolism Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anakinra Prefilled SyringeDrug
Also called Kineret
Subcutaneous injection of 100 mg/ 0.67 ml of Kineret or placebo
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: Anakinra Prefilled Syringe |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 10 minutes
Secondary outcomes (12)
Change of C-peptide
Plasma level of c-peptide before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
Change of insulin
Plasma level of insulin before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
Change of glucose
Plasma level of glucose before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
Change of glucagon
Plasma level of glucagon before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
Change of GLP-1
Plasma level of GLP-1 before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
Change of pancreatic polypeptide
Plasma level of pancreatic polypeptide before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
Change of IL-1β
Plasma level of IL-1β before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
Change of IL-6
Plasma level of IL-6 before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
Change of IL-1Ra
Plasma level of IL-1Ra before and after a meal through nasogastric tube or with anakinra or placebo after a standardized meal.
Measured: 6 hours
Change of TNFa
Plasma level of TNFa before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
change in hunger
Visual analogue scale (VAS) for hunger (from minimum value = not hungry at all to maximum value = extremely hungry) before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
Change in autonomic function
Change in heart-rate variability during a continuous ECG as indirect measure of measure of the autonomic function before and after a standardized meal after acute treatment or repeated treatment with anakinra or placebo. Repeated Treatment applies only to anakinra and to Group 2.
Measured: 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2020
- Study start13 Jan 2020
- Primary completion28 May 2024
- Study completion28 May 2024
Why it stopped: Too low recruitment in group with patients with diabetes.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus Type 2 in ObeseStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marc Y Donath, Prof. Dr. MD, Principal investigator, University of Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04227769
- Sponsor's protocol ID
- EKNZ 2019-02307
- Acronym
- Cephalira
- Status last verified
- Jan 2025
- First submitted
- 7 Jan 2020
- Last updated
- 29 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IL-1-receptor Antagonist During Cephalic Phase of Insulin Secretion in Health and Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT04227769
- Acronym / sponsor ID
- Cephalira / EKNZ 2019-02307
- Conditions
- Diabetes Mellitus Type 2 in Obese, Inflammation, Metabolic Disease, Glucose Metabolism Disorders (Including Diabetes Mellitus)
- Keywords
- anakinra, cephalic phase of insulin secretion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Too low recruitment in group with patients with diabetes.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 13 Jan 2020 (actual)
- Primary completion
- 28 May 2024 (actual)
- Study completion
- 28 May 2024 (actual)
- First posted
- 14 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The role of the immune system in metabolism has been extensively investigated in pancreatic islets and insulin sensitive tissues. However little attention has been given to a potential role of the innate immune system in the cephalic phase of insulin secretion. In humans, the cephalic phase of insulin secretion appear reduced in obesity and in patients with type 2 diabetes.
In this prospective, randomized, mixed double- and single-blinded, placebo-controlled, cross-over clinical trial we aim 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).
Group 1: After screening, subjects will be randomized to 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. The study will be performed in a population of healthy individuals.
Group 2: Same as for Group 1 with the following addition: 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.
Healthy subjects from group 1 will be matched for sex and age to the diabetic cohort from group 2.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| healthy individuals | Experimental | Drug: Anakinra Prefilled SyringeTwo 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) |
| obese patients with type 2 diabetes | Experimental | Drug: Anakinra Prefilled SyringeThree 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) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.)
- No apparent disease requiring medication
- BMI < 25 kg/ m2
- C-reactive protein ≤ 2 mg/L
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anakinra Prefilled SyringeAlso: KineretSubcutaneous injection of 100 mg/ 0.67 ml of Kineret or placebo | Drug | healthy individuals, obese patients with type 2 diabetes |
Primary outcome
Change in insulin concentration in blood during the cephalic phase of insulin secretion in healthy individuals
Time frame: 10 minutes
Insulin concentration in blood at 0, 3,6 and 10 minutes after ingestion of a standardized meal in healthy individuals.
Change in insulin concentration in blood during the cephalic phase of insulin secretion in obese patients with type 2 diabetes
Time frame: 10 minutes
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.
12 secondary outcomes
Change of C-peptide
Time frame: 6 hours
Change of insulin
Time frame: 6 hours
Change of glucose
Time frame: 6 hours
Change of glucagon
Time frame: 6 hours
Change of GLP-1
Time frame: 6 hours
Change of pancreatic polypeptide
Time frame: 6 hours
Change of IL-1β
Time frame: 6 hours
Change of IL-6
Time frame: 6 hours
Change of IL-1Ra
Time frame: 6 hours
Change of TNFa
Time frame: 6 hours
change in hunger
Time frame: 6 hours
Change in autonomic function
Time frame: 6 hours
Results and safety
The study was stopped early (reason given: Too low recruitment in group with patients with diabetes.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Y Donath, Prof. Dr. MD principal investigator
University of Basel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anakinra Prefilled Syringe in people with Diabetes Mellitus Type 2 in Obese and Inflammation, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Too low recruitment in group with patients with diabetes.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in insulin concentration in blood during the cephalic phase of insulin secretion in healthy individuals (time frame: 10 minutes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2025.