Diabetes MellitusPhase 2NCT01285245
Effect of Anakinra on Insulin Sensitivity in Type 1 Diabetes Mellitus
A Phase 2 study testing kineret in people with Diabetes Mellitus, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
The purpose of this study is to test whether anakinra is able to reduce insulin resistance. This will be tested in overweighted type I diabetes mellitus patients, which have no residual beta-cell function. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- kineret
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2011to Dec 2011
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes for more than 5 years
- Body mass index of > 25 kg/m2
- Insulin requirement > 0.5 U/kg bodyweight
- HbA1c>7.5%, stable glycemic control
Who cannot join
- Inability to give informed consent
- Presence of any medical condition that might interfere with the current study protocol.
- Immunodeficiency or immunosuppressive treatment (including TNFα blocking agents and corticosteroids)
- Anti-inflammatory drugs (including nonsteroidal anti-inflammatory drugs, 100 mg or less of aspirin per day is allowed)
- Signs of current infection (fever, C-reactive protein (CRP) > 30 mmol/l, treatment with antibiotics, previous or current diagnosis of tuberculosis.
- A history of recurrent infections
Show all 10Show fewer
- Pregnancy or breast-feeding (contraception of at least 3 months before inclusion is required for fertile women)
- Liver disease (aspartate aminotransferase or alanine aminotransferase level of more than three times the upper limit of normal range)
- Renal disease (creatinine > 130 µmol/l
- Neutropenia < 2 x 109/l
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Radboud University Nijmegen Medical Centre
Nijmegen, 6500HB
About this study
Official title: Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Type 1 Diabetes Mellitus.
The purpose of this study is to test whether anakinra is able to reduce insulin resistance.
This will be tested in overweighted type I diabetes mellitus patients, which have no residual beta-cell function. By using this patient group, all positive effects on glycemic control should be the consequence of improved insulin sensitivity.
Read the detailed description
Although typically associated with type 2 diabetes, insulin resistance has been documented in Type 1 diabetes. Insulin resistance may also play an important role in the pathophysiology of type 1 diabetes mellitus. Once diabetes has emerged chronically elevated glucose levels further induce insulin resistance (glucose toxicity).
Inflammation is an important link between obesity and insulin resistance. The mechanism of hyperglycemia-induced insulin resistance is not clear, but evidently must be related to high glucose levels. There are indications that chronic hyperglycemia can induce inflammation, for example hyperglycemia induces IL-1β release, and recent studies have shown an interaction with thioredoxin interacting protein (TXNIP), at the level of the beta-cell but also, as found by our own group, at the level of the adipose tissue
All together, these findings suggest that blocking IL-1β-receptor activation by the interleukin-1 receptor antagonist anakinra, may reverse insulin resistance associated both with obesity and/or chronic hyperglycemia. When applied in (hyperglycemic) subjects with type 2 diabetes, blocking IL-1β should diminish the effects of glucose toxicity both at the level of beta-cell function as at the level of insulin sensitivity. When applied in (hyperglycemic) subjects with type 1 diabetes, the effects of glucose toxicity at the level of insulin sensitivity should decrease.
In order to be able to study an isolated effect of IL-1β blockade on insulin sensitivity, this study will test this hypothesis in subjects with type 1 diabetes and hence provide a proof of principle in vivo in humans for a proposed link between hyperglycemia, inflammation and insulin resistance.
- Conditions
- Diabetes Mellitus
- Being tested
- kineret
- Keywords
- insulin sensitivity, interleukin-1 receptor antagonist, inflammation, hyperglycemia-induced insulin resistance
- Medical subject headings
- Diabetes Mellitus, Insulin Resistance, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
kineretDrug
Also called anakinra, interleukin-1 receptor antagonist
once daily 100 mg of kineret subcutaneously for 8 days
| Study group | Role | What they receive |
|---|---|---|
| kineret | Experimental | Not described Receives: Drug: kineret |
What is being measured
The primary outcome is the main question the study is designed to answer.
insulin sensitivity as determined by euglycemic hyperinsulinemic clamp
insulin sensitivity measured by euglycemic hyperinsulinemic clamp
Measured: change in insulin sensitivity after 1 week of treatment with anakinra as compared to baseline
Secondary outcomes (4)
glycemic control
HbA1c, fasting glucose
Measured: baseline, after 1 week of treatment and 4 weeks after treatment termination
adipocyte insulin sensitivity
Measured: baseline, after 1 week of treatment, 4 weeks after treatment termination
circulating hormonal and inflammatory factors and lipid profile
Measured: baseline, after 1 week of treatment, 4 weeks after treatment termination
insulin sensitivity as determined by euglycemic hyperinsulinemic clamp
insulin sensitivity measured by euglycemic hyperinsulinemic clamp
Measured: change in insulin sensitivity 4 weeks after stopping anakinra treatment as compared to baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2011 (estimated)
- Study startApr 2011
- Primary completionSep 2011 (estimated)
- Study completionDec 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Cees J Tack, MD PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01285245
- Sponsor's protocol ID
- NL34377.091.10
- Other IDs
- 2010-023479-24
- Status last verified
- Nov 2010
- First submitted
- 26 Nov 2010
- Last updated
- 14 Apr 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Type 1 Diabetes Mellitus.
- ClinicalTrials.gov ID
- NCT01285245
- Acronym / sponsor ID
- NL34377.091.10
- Conditions
- Diabetes Mellitus
- Keywords
- insulin sensitivity, interleukin-1 receptor antagonist, inflammation, hyperglycemia-induced insulin resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Sep 2011 (estimated)
- Study completion
- Dec 2011 (estimated)
- First posted
- 27 Jan 2011 (estimated)
- 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.
The purpose of this study is to test whether anakinra is able to reduce insulin resistance.
This will be tested in overweighted type I diabetes mellitus patients, which have no residual beta-cell function. By using this patient group, all positive effects on glycemic control should be the consequence of improved insulin sensitivity.
Detailed description
Although typically associated with type 2 diabetes, insulin resistance has been documented in Type 1 diabetes. Insulin resistance may also play an important role in the pathophysiology of type 1 diabetes mellitus. Once diabetes has emerged chronically elevated glucose levels further induce insulin resistance (glucose toxicity).
Inflammation is an important link between obesity and insulin resistance. The mechanism of hyperglycemia-induced insulin resistance is not clear, but evidently must be related to high glucose levels. There are indications that chronic hyperglycemia can induce inflammation, for example hyperglycemia induces IL-1β release, and recent studies have shown an interaction with thioredoxin interacting protein (TXNIP), at the level of the beta-cell but also, as found by our own group, at the level of the adipose tissue
All together, these findings suggest that blocking IL-1β-receptor activation by the interleukin-1 receptor antagonist anakinra, may reverse insulin resistance associated both with obesity and/or chronic hyperglycemia. When applied in (hyperglycemic) subjects with type 2 diabetes, blocking IL-1β should diminish the effects of glucose toxicity both at the level of beta-cell function as at the level of insulin sensitivity. When applied in (hyperglycemic) subjects with type 1 diabetes, the effects of glucose toxicity at the level of insulin sensitivity should decrease.
In order to be able to study an isolated effect of IL-1β blockade on insulin sensitivity, this study will test this hypothesis in subjects with type 1 diabetes and hence provide a proof of principle in vivo in humans for a proposed link between hyperglycemia, inflammation and insulin resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| kineret | Experimental | Drug: kineret |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Type 1 diabetes for more than 5 years
- Body mass index of > 25 kg/m2
- Insulin requirement > 0.5 U/kg bodyweight
- HbA1c>7.5%, stable glycemic control
Key exclusion criteria (10 listed)
- Inability to give informed consent
- Presence of any medical condition that might interfere with the current study protocol.
- Immunodeficiency or immunosuppressive treatment (including TNFα blocking agents and corticosteroids)
- Anti-inflammatory drugs (including nonsteroidal anti-inflammatory drugs, 100 mg or less of aspirin per day is allowed)
- Signs of current infection (fever, C-reactive protein (CRP) > 30 mmol/l, treatment with antibiotics, previous or current diagnosis of tuberculosis.
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 |
|---|---|---|
| kineretAlso: anakinra, interleukin-1 receptor antagonistonce daily 100 mg of kineret subcutaneously for 8 days | Drug | kineret |
Primary outcome
insulin sensitivity as determined by euglycemic hyperinsulinemic clamp
Time frame: change in insulin sensitivity after 1 week of treatment with anakinra as compared to baseline
insulin sensitivity measured by euglycemic hyperinsulinemic clamp
4 secondary outcomes
glycemic control
Time frame: baseline, after 1 week of treatment and 4 weeks after treatment termination
adipocyte insulin sensitivity
Time frame: baseline, after 1 week of treatment, 4 weeks after treatment termination
circulating hormonal and inflammatory factors and lipid profile
Time frame: baseline, after 1 week of treatment, 4 weeks after treatment termination
insulin sensitivity as determined by euglycemic hyperinsulinemic clamp
Time frame: change in insulin sensitivity 4 weeks after stopping anakinra treatment as compared to baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2011.
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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.
Cees J Tack, MD PhD principal investigator
Radboud University Medical Center
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 kineret in people with Diabetes Mellitus, run by Radboud University Medical Center at 1 site in Netherlands.
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 4 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 14 Apr 2011. 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 Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Edwin JP van Asseldonk, MD (+31243619857, e.vanasseldonk@aig.umcn.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
insulin sensitivity as determined by euglycemic hyperinsulinemic clamp (time frame: change in insulin sensitivity after 1 week of treatment with anakinra as compared to baseline). 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 14 Apr 2011.