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Type 2 DiabetesPhase 2NCT00303394

Treatment of Patients With Type 2 Diabetes With an Interleukin-1 Antagonist

A Phase 2 study testing IL-1Ra in people with Type 2 Diabetes, run by University of Zurich at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Aim: To investigate the therapeutic potential of IL-1Ra in type 2 diabetes. Rationale: Since the major defect leading to a decrease in b-cell mass in type 2 diabetes is increased apoptosis, therapeutic approaches designed to arrest apoptosis could be a significant new development in its management. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Type 2 Diabetes
What is being tested?
IL-1Ra
How many people
72 participants
Where
2 sitesin 2 countries
Study dates
Apr 2004to Mar 2006
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >20
  • Diabetes mellitus Type 2 (American Diabetes Association criteria) of at least 3 months duration
  • HbA1c >7.5%
  • Body-mass index (BMI) > 27

Who cannot join

  • Positive GAD 65 or IA-2 antibodies at inclusion.
  • HbA1c >12%, polyuria and thirst (exclusion of severely decompensated patients)
  • C-peptide < 400pmol/l (basal )
  • Established anti-inflammatory therapy (includiung cortisone, NSAID, Cox-2-inhibitor). Low dose aspirin (£ 100mg) will be tolerated.
  • CRP >30 mg/dl, fever, current treatment with antibiotics, or chronic granulomatous infections (e.g. tuberculosis) in the history or on a screening chest X-ray.
  • Neutropenia or anemia (leucocyte count < 2.0x109 /l, hemoglobin <11g/dl for ma les or <10g/dl for females)
Show all 11Show fewer
  • Pregnancy or breast-feeding. When appropriate (fertile women),anticonception for at last 3 month prior inclusion will be required.
  • Severe liver or renal disease ( AST or ALT>3 times the upper limit of normal laboratory range, serum creatinine >130mM)
  • Ongoing malignant neoplasm
  • Use of any investigational drug within 30 days of enrollment into the study or within 5 half-lives of the investigational drug (whichever is longer)
  • Immunosuppressive treatment or immunodeficient diseases.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Denmark1 site

  • Steno Diabetes Center

    Gentofte Municipality, Copenhagen, 2280

Other trials in Denmark

Switzerland1 site

  • University Hospital of Zurich, Division of Endocrinology and Diabetes

    Zurich, Canton of Zurich, 8091

Other trials in Switzerland

About this study

Official title: Phase 2 Study of IL-1Ra in Patients With Type 2 Diabetes

Aim: To investigate the therapeutic potential of IL-1Ra in type 2 diabetes.

Rationale: Since the major defect leading to a decrease in b-cell mass in type 2 diabetes is increased apoptosis, therapeutic approaches designed to arrest apoptosis could be a significant new development in its management. This approach might actually reverse the disease to a degree rather than just palliate glycemia. Based on current thinking, treatment with IL-1Ra appears as a promising approach. The prospected effect is blocking of the IL-1b-mediated glucotoxicity and thereby to prevent the decline in b-cell mass, together with a rapid restoration of b-cell function. FDA approval for IL-1Ra in the treatment of rheumatoid arthritis occurred based on a favourable tolerability profile.

Read the detailed description

Methodology: This will be a two-centre (University Hospital, Zurich, Switzerland and Steno Diabetes Center, Gentofte, Denmark) study. 72 patients will be randomised according to a double-blind, placebo-controlled protocol in which half of the patients are treated with IL-1Ra, the other half with saline. The treatment period will last 13 weeks. This time-period should be sufficient for reversal of functional glucotoxicity and feasible in terms of patient compliance. Whether 13 weeks of treatment will be sufficient to make significant changes in b-cell mass in unpredictable. However, blocking b-cell apoptosis, while new islet formation and b-cell replication are normal, may initiate enlargement of b-cell mass, which may progress beyond the treatment period. Patient evaluation will be performed at start and after 4, 13, 26, 39 and 52 weeks. Following 13 weeks, patients with a fasting plasma glucose levels > 8 mM or with a glycosylated hemoglobin level (HbA1c) > 8% will be treated with insulin. Insulin treatment will not be initiated earlier to avoid interference with possible effects of insulin on primary outcome in the period where the largest effect of IL-1Ra are expected. To assess effects of IL-1Ra on insulin sensitivity, a subset of 40 patients (20 IL-1Ra- and 20 placebo-treated) will undergo an euglycemic-hyperinsulinemic clamp as well as a muscle and fat biopsy at start and after the end of treatment (13 weeks). The Ethics Committee of both centres have already approved the procedure.

Conditions
Type 2 Diabetes
Being tested
IL-1Ra
Keywords
Type 2 Diabetes, IL-1, inflammation, glucotoxicity, insulin
Medical subject headings
Diabetes Mellitus, Type 2, Inflammation, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IL-1RaDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. HbA1c

Secondary outcomes (7)

  1. Insulin requirement

  2. Stimulated C peptide and insulin

  3. Fasting plasma glucose (FPG)

  4. Serum cytokine levels, CRP

  5. Insulin secretion and Insulin-sensitivity index derived from an OGTT with insulin and glucose measurements.

  6. In a subgroup of patients, insulin-sensitivity assessed by clamp techniques

  7. Insulin signaling- and cytokine- gene expression profiles derived from muscle and fat biopsy samples.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Mar 2006 (estimated)
  2. Study startApr 2004
  3. Study completionMar 2006

Resources

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
Factorial
Masking
Double blind
Enrolment
72 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00303394
Sponsor's protocol ID
EK-1000-ZH
Status last verified
Mar 2007
First submitted
14 Mar 2006
Last updated
5 Mar 2007
Results posted
No

Publications

  • de Baat A, Trinh B, Ellingsgaard H, Donath MY. Physiological role of cytokines in the regulation of mammalian metabolism. Trends Immunol. 2023 Aug;44(8):613-627. doi: 10.1016/j.it.2023.06.002. Epub 2023 Jul 7.

    PubMed 37423882

  • 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 17429083

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IL-1Ra in people with Type 2 Diabetes, run by University of Zurich at 2 sites in 2 countries.

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 11 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: finished, as of the sponsor's last update on 5 Mar 2007. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Denmark, 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

HbA1c. 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 NCT00303394, 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 5 Mar 2007.

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