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

March 2, 2007 updated by: University of Zurich

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

72

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Copenhagen
      • Gentofte, Copenhagen, Denmark, 2280
        • Steno Diabetes center
  • Switzerland
      • Zurich, Switzerland, 8091
        • University Hospital of Zurich, Division of Endocrinology and Diabetes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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)
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
HbA1c

Secondary Outcome Measures

Outcome Measure
Fasting plasma glucose (FPG)
Insulin requirement
Stimulated C peptide and insulin
Serum cytokine levels, CRP
Insulin secretion and Insulin-sensitivity index derived from an OGTT with insulin and glucose measurements.
In a subgroup of patients, insulin-sensitivity assessed by clamp techniques
Insulin signaling- and cytokine- gene expression profiles derived from muscle and fat biopsy samples.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Zurich

Collaborators

Steno Diabetes Center Copenhagen

Investigators

  • Study Chair: Marc Y Donath, MD, University of Zurich

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2004

Study Completion

March 1, 2006

Study Registration Dates

First Submitted

March 14, 2006

First Submitted That Met QC Criteria

March 14, 2006

First Posted (Estimate)

March 16, 2006

Study Record Updates

Last Update Posted (Estimate)

March 5, 2007

Last Update Submitted That Met QC Criteria

March 2, 2007

Last Verified

March 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EK-1000-ZH

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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