Diabetes Mellitus, Type 2Phase 2NCT00928876
Interleukin-1 Receptor Antagonist and Insulin Sensitivity
A Phase 2 study testing Anakinra (Kineret) in people with Diabetes Mellitus, Type 2 and Insulin Resistance, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Obesity is characterized by continuous low-grade inflammation. This is an important link between obesity and insulin resistance. Results from the investigators' own group of in vitro and in vivo research on mice show that Interleukin-1 is involved in the process of developing insulin resistance. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2, Insulin Resistance
- What is being tested?
- Anakinra (Kineret)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Jun 2009to Jul 2010
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- adult subjects with a BMI > 30 kg/m2
- 3 or more characteristics of the metabolic syndrome
Who cannot join
- inability to give informed consent
- age < 18 years
- known diabetes mellitus
- fasting plasma glucose > 7,0 mmol/l or HbA1c > 6,2%
- presence of any medical condition that might interfere with the current study protocol
- immunodeficiency of immunosuppressive treatment
Show all 13Show fewer
- anti-inflammatory drugs (100 mg of aspirin/day is allowed)
- signs of current infection
- history of recurrent infections
- pregnancy or breast feeding
- liver disease
- renal disease
- neutropenia
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Rabdoud University Nijmegen Medical Centre
Nijmegen, 6500 HB
About this study
Official title: Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Obese, Insulin Resistant Individuals
Obesity is characterized by continuous low-grade inflammation. This is an important link between obesity and insulin resistance.
Results from the investigators' own group of in vitro and in vivo research on mice show that Interleukin-1 is involved in the process of developing insulin resistance. Earlier it has been shown that interleukin-1 receptor antagonist in human subjects improves glycemic control. The investigators' hypothesis is that this is due to improved insulin sensitivity.
Read the detailed description
The prevalence of obesity is increasing fast. Obesity is one of the most common acquired risk factors for insulin resistance. As a consequence the prevalence of type 2 diabetes mellitus is rising fast as well.
Interleukin 6 and Tumor Necrosis Factor alfa are well known pro-inflammatory cytokines that have been linked to insulin resistance. Results from our own group show that interleukin-1 is also involved in the process of developing insulin resistance.
Earlier research projects studied the effect of Interleukin-1 receptor antagonist (Anakinra) on glycemic control in subjects with type 2 diabetes mellitus. It was shown that glycemic control was improved. The authors conclude that this is the result of improved function of pancreatic beta cells.
These results are in contrast to our results of in vitro en in vivo research on mice, which show improved insulin sensitivity by Interleukin-1 receptor antagonist.
A possible explanation for not finding an effect on insulin sensitivity by earlier research projects may be that it is difficult to reliable quantify insulin sensitivity in this group of patients with concurrent changes in glycemic control, extensive co-morbidity and medication use, who might be at the rather extreme end of insulin resistance. Furthermore a relatively low dose of Anakinra was used.
Altogether we hypothesize that the effect of Interleukin-1 is not only mediated through better pancreatic beta-cell function, but that Interleukin-1 blocking by recombinant Interleukin-1 receptor antagonist will also diminish insulin resistance.
- Conditions
- Diabetes Mellitus, Type 2, Insulin Resistance
- Being tested
- Anakinra (Kineret), Placebo
- Keywords
- anakinra, Diabetes mellitus, type 2, Insulin resistance, Interleukin-1beta
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anakinra (Kineret)Drug
Also called kineret
anakinra 150 mg s/c. daily for four weeks
PlaceboDrug
placebo s/c daily for four weeks
| Study group | Role | What they receive |
|---|---|---|
| Anakinra group | Experimental | Anakinra 150 mg/day during four weeks Receives: Drug: Anakinra (Kineret) |
| Placebo | Placebo comparator | Placebo during four weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
to determine the effect of Interleukin-1 receptor antagonist on insulin sensitivity, as derived from glucose infusion rate measured by euglycemic hyperinsulinemic clamp
Measured: after four weeks of treatment
Secondary outcomes (3)
pancreatic beta cell function als tested by oral glucose tolerance test, pro-insulin/insulin ratio
Measured: after four weeks of treatment
lipid profile
Measured: after four weeks of treatment
systemic inflammation
Measured: after four weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2009 (estimated)
- Study startJun 2009
- Primary completionMar 2010 (estimated)
- Study completionJul 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- C J Tack, Prof Dr, Study chair, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00928876
- Sponsor's protocol ID
- UMCN001
- Status last verified
- Jun 2009
- First submitted
- 25 Jun 2009
- Last updated
- 17 Dec 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007 Apr 12;356(15):1517-26. doi: 10.1056/NEJMoa065213.
PubMed 17429083van Asseldonk EJ, Stienstra R, Koenen TB, Joosten LA, Netea MG, Tack CJ. Treatment with Anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2011 Jul;96(7):2119-26. doi: 10.1210/jc.2010-2992. Epub 2011 Apr 20.
PubMed 21508140
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2010. 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 Obese, Insulin Resistant Individuals
- ClinicalTrials.gov ID
- NCT00928876
- Acronym / sponsor ID
- UMCN001
- Conditions
- Diabetes Mellitus, Type 2, Insulin Resistance
- Keywords
- anakinra, Diabetes mellitus, type 2, Insulin resistance, Interleukin-1beta
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Mar 2010 (estimated)
- Study completion
- Jul 2010 (estimated)
- First posted
- 26 Jun 2009 (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.
Obesity is characterized by continuous low-grade inflammation. This is an important link between obesity and insulin resistance.
Results from the investigators' own group of in vitro and in vivo research on mice show that Interleukin-1 is involved in the process of developing insulin resistance. Earlier it has been shown that interleukin-1 receptor antagonist in human subjects improves glycemic control. The investigators' hypothesis is that this is due to improved insulin sensitivity.
Detailed description
The prevalence of obesity is increasing fast. Obesity is one of the most common acquired risk factors for insulin resistance. As a consequence the prevalence of type 2 diabetes mellitus is rising fast as well.
Interleukin 6 and Tumor Necrosis Factor alfa are well known pro-inflammatory cytokines that have been linked to insulin resistance. Results from our own group show that interleukin-1 is also involved in the process of developing insulin resistance.
Earlier research projects studied the effect of Interleukin-1 receptor antagonist (Anakinra) on glycemic control in subjects with type 2 diabetes mellitus. It was shown that glycemic control was improved. The authors conclude that this is the result of improved function of pancreatic beta cells.
These results are in contrast to our results of in vitro en in vivo research on mice, which show improved insulin sensitivity by Interleukin-1 receptor antagonist.
A possible explanation for not finding an effect on insulin sensitivity by earlier research projects may be that it is difficult to reliable quantify insulin sensitivity in this group of patients with concurrent changes in glycemic control, extensive co-morbidity and medication use, who might be at the rather extreme end of insulin resistance. Furthermore a relatively low dose of Anakinra was used.
Altogether we hypothesize that the effect of Interleukin-1 is not only mediated through better pancreatic beta-cell function, but that Interleukin-1 blocking by recombinant Interleukin-1 receptor antagonist will also diminish insulin resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anakinra group | Experimental | Drug: Anakinra (Kineret)Anakinra 150 mg/day during four weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo during four weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- adult subjects with a BMI > 30 kg/m2
- 3 or more characteristics of the metabolic syndrome
Key exclusion criteria (13 listed)
- inability to give informed consent
- age < 18 years
- known diabetes mellitus
- fasting plasma glucose > 7,0 mmol/l or HbA1c > 6,2%
- presence of any medical condition that might interfere with the current study protocol
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 (Kineret)Also: kineretanakinra 150 mg s/c. daily for four weeks | Drug | Anakinra group |
| Placeboplacebo s/c daily for four weeks | Drug | Placebo |
Primary outcome
to determine the effect of Interleukin-1 receptor antagonist on insulin sensitivity, as derived from glucose infusion rate measured by euglycemic hyperinsulinemic clamp
Time frame: after four weeks of treatment
3 secondary outcomes
pancreatic beta cell function als tested by oral glucose tolerance test, pro-insulin/insulin ratio
Time frame: after four weeks of treatment
lipid profile
Time frame: after four weeks of treatment
systemic inflammation
Time frame: after four weeks of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2010.
- Background: PubMed 17429083Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007 Apr 12;356(15):1517-26. doi: 10.1056/NEJMoa065213.
- Derived from this study: PubMed 21508140van Asseldonk EJ, Stienstra R, Koenen TB, Joosten LA, Netea MG, Tack CJ. Treatment with Anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2011 Jul;96(7):2119-26. doi: 10.1210/jc.2010-2992. Epub 2011 Apr 20.
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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.
C J Tack, Prof Dr study chair
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 Anakinra (Kineret) in people with Diabetes Mellitus, Type 2 and Insulin Resistance, 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 2 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: status not confirmed, as of the sponsor's last update on 17 Dec 2010. 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. Some participants in this study may receive a placebo. 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?
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?
to determine the effect of Interleukin-1 receptor antagonist on insulin sensitivity, as derived from glucose infusion rate measured by euglycemic hyperinsulinemic clamp (time frame: after four weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00928876, which also lists 2 linked publications.
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 17 Dec 2010.