Anti-Interleukin-1 in Diabetes Action

NCT ID: NCT00711503

Last Updated: 2012-09-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

69 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-01-31

Study Completion Date

2012-06-30

Brief Summary

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A draw trial of the effect of Interleukin-1 Receptor Antagonist (anakinra, Kineret®) on the insulin production in patients with new onset Type 1 diabetes.

Kineret® is already being used in the treatment of patients suffering from rheumatoid arthritis and preclinical studies are now suggesting that it may also be useful for patients with Type 1 diabetes. The active substance in Kineret is interleukin-1 receptor antagonist, a blocker of an immune-signal molecule named interleukin-1.

The trial is a blinded randomised trial, in which the patient is allocated to receive the active drug (Kineret®) or placebo (saline). The hypothesis is that anti-IL-1 treatment as add-on therapy to conventional insulin therapy will preserve or enhance beta-cell function.

Detailed Description

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Objectives:

The aim of the Anti-Interleukin-1 in Diabetes Action trial (AIDA) study is to test the feasibility, safety/tolerability and potential efficacy of anti-IL-1 therapy in maintaining or enhancing beta-cell function in people with new onset Type 1 diabetes.

Trial Design:

A randomized, placebo controlled, double masked, parallel group, multicentre trial of IL-1 antagonism in subjects with newly-diagnosed Type 1 diabetes. Patients are instructed to inject 100 mg human recombinant interleukin-1 receptor antagonist (anakinra, Kineret®, Amgen, CA) or placebo s.c. once daily for 2 years. Endpoints will be evaluated every three months, with an interim analysis after 6 months.

Trial population:

The design will be a two-stage phase 2a study to address feasibility, safety/tolerability and potential efficacy. In the first phase 80 patients between 18 and 35 years of age with new on-set Type 1 diabetes will be randomized to anakinra or placebo, and endpoints will be analyzed as an interim analysis after 6 months by an independent data and safety monitoring board (DSMB). A futility analysis will be performed at this time point to prevent continuation of the trial if it shows no likelihood of demonstrating efficacy. In the event the trial does show promise of efficacy considering the power of the first phase based on a conditional analysis the DSMB can recommend prolongation of the study with recruitment to ensure adequate power, and that additional funding is provided.

Methods and interventions:

The patients are instructed to administer anti-IL-1 therapy in the form of recombinant human non-glycosylated interleukin-1 receptor antagonist (anakinra) at a dose of 100 mg once daily or placebo by subcutaneous injection at the same time-point in the morning. Primary and secondary endpoints and safety parameters are investigated after 1 month and then every 3 months.

Safety:

Anakinra is FDA approved for the indication rheumatoid arthritis and has an acceptable risk / benefit profile in this indication, with more than 100.000 patients treated. Most common ad-verse events include mild and transient local injection reactions in 20-50% of subjects treated with Anakinra. Consistent with its mechanism of action, anakinra reduces WBC/ANC in 2.4% of patients and this may increase the risk of infection. Accordingly, treatment with anakinra will not be initiated in patients with active infections. Safety will be monitored by physical exams and blood and urine tests.

Conditions

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Type 1 Diabetes

Keywords

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endogenous insulin production C-peptide level insulin requirement

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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2

The patients are instructed to administer placebo by subcutaneous injection

Group Type PLACEBO_COMPARATOR

saline

Intervention Type DRUG

The patients are instructed to administer placebo (saline) once daily by subcutaneous injection

1

The patients are instructed to administer anti-IL-1 therapy in the form of recombinant human non-glycosylated interleukin-1 receptor antagonist (IL-1Ra, anakinra, Kineret®, Amgen, CA, USA) \[13\] at a dose of 100 mg once daily by subcutaneous injection

Group Type EXPERIMENTAL

anakinra

Intervention Type DRUG

The patients are instructed to administer anti-IL-1 therapy in the form of recombinant human non-glycosylated interleukin-1 receptor antagonist (IL-1Ra, anakinra, Kineret®, Amgen, CA, USA) \[13\] at a dose of 100 mg once daily by subcutaneous injection

Interventions

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anakinra

The patients are instructed to administer anti-IL-1 therapy in the form of recombinant human non-glycosylated interleukin-1 receptor antagonist (IL-1Ra, anakinra, Kineret®, Amgen, CA, USA) \[13\] at a dose of 100 mg once daily by subcutaneous injection

Intervention Type DRUG

saline

The patients are instructed to administer placebo (saline) once daily by subcutaneous injection

Intervention Type DRUG

Other Intervention Names

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Kineret

Eligibility Criteria

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Inclusion Criteria

* Type 1 diabetes diagnosed according to WHO 1999 criteria
* Positive GAD auto-antibodies
* Age 18-35 yrs at onset of diabetes
* Time from first symptoms of diabetes \< 12 weeks
* Peak C-peptide more than or equal to 200 pM after a standardized mixed meal test (Boost) at a test carried out when the subject is metabolically stable, i.e. after resolution of any polyuria, polydypsia or ketoacidosis.

Exclusion Criteria

* Severe liver or renal disease (creatinine \> 100 μmol/L, ASAT/ALAT \> 2\* ULN, alkaline phosphatase \> 2 \* ULN)
* History of heart disease, signs of cardiac failure or abnormal ECG
* Present or previous malignancy
* Pregnancy or failure of fertile female to comply with contraceptional planning, or breast-feeding. (Safe contraceptive methods include birth control pills, IUD, and gestagen implants) . Plans of pregnancy within 2 years.
* Participation in other clinical intervention studies
* Anti-inflammatory therapy (except aspirin £ 100 mg/d)
* Active infections (CRP\>30), history of recurrent infection or predisposition to infections
* Neutropenia: ANC \< 1.5\*109/L, or anaemia: Haemoglobin \< 8.0 g/dL
* Immune-suppressive treatment or immune-deficiency
* Presence at diagnosis of late diabetic complications
* Concurrent vaccination with live vaccine. Known need for live vaccinations within 2 years.
* Use of Etanercept within 6 months before screening or during the double-blinded study period
* Hypersensitivity to E. coli-derived proteins, anakinra or any components of the product.
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Juvenile Diabetes Research Foundation

OTHER

Sponsor Role collaborator

Oeresund Diabetes Academy

UNKNOWN

Sponsor Role collaborator

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role lead

Responsible Party

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Lise Tarnow

professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thomas R Mandrup-Poulsen, MD, DMSc

Role: PRINCIPAL_INVESTIGATOR

Steno Diabetes Center Copenhagen

Marc Donath

Role: STUDY_DIRECTOR

Universtity of Zürich

Flemming Pociot, DMSc

Role: STUDY_DIRECTOR

Steno Diabetes Center Copenhagen

Charles Dinarello

Role: STUDY_DIRECTOR

University of Colorado Health Science Center

Edwin Gale, Professor

Role: STUDY_CHAIR

Bristol University, UK

Locations

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Aalborg Hospital

Aalborg, , Denmark

Site Status

Aarhus Universitetshospital

Aarhus, , Denmark

Site Status

Bispebjerg Universitetshospital

Copenhagen, , Denmark

Site Status

Steno Diabetes Center

Gentofte Municipality, , Denmark

Site Status

Nordsjællands Hospital, Hillerød

Hillerød, , Denmark

Site Status

Ulm University, Dept. of Internal Medicine

Ulm, Donau, Germany

Site Status

Leibniz Center for Diabetes research, Heinrich-Heine University

Düsseldorf, , Germany

Site Status

University of Frankfurt am Main

Frankfurt am Main, , Germany

Site Status

Institut für Diabetesforschung, Munich University of Technology

Munich, , Germany

Site Status

University Campus Bio-Medico

Rome, , Italy

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

Medical University of Bialystok

Bialystok, , Poland

Site Status

Hospital de Cruces, Diabetes Research Group

Barakaldo, Bizkaia, Spain

Site Status

Hospital Unversitario Insular de Gran Canaria

Las Palmas, Gran Canaria, Spain

Site Status

Hospital Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Arnua de Vilanova

Lleida, , Spain

Site Status

University Hospital Zürich

Zurich, , Switzerland

Site Status

Countries

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Hungary Lithuania Slovenia Sweden Denmark Germany Italy Netherlands Poland Spain Switzerland

References

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Pickersgill LM, Mandrup-Poulsen TR. The anti-interleukin-1 in type 1 diabetes action trial--background and rationale. Diabetes Metab Res Rev. 2009 May;25(4):321-4. doi: 10.1002/dmrr.960.

Reference Type BACKGROUND
PMID: 19405081 (View on PubMed)

Moran A, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Greenbaum CJ, Herold KC, Marks JB, Raskin P, Sanda S, Schatz D, Wherrett DK, Wilson DM, Krischer JP, Skyler JS; Type 1 Diabetes TrialNet Canakinumab Study Group; Pickersgill L, de Koning E, Ziegler AG, Boehm B, Badenhoop K, Schloot N, Bak JF, Pozzilli P, Mauricio D, Donath MY, Castano L, Wagner A, Lervang HH, Perrild H, Mandrup-Poulsen T; AIDA Study Group. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet. 2013 Jun 1;381(9881):1905-15. doi: 10.1016/S0140-6736(13)60023-9. Epub 2013 Apr 5.

Reference Type DERIVED
PMID: 23562090 (View on PubMed)

Other Identifiers

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EudraCT 2007-007146-34

Identifier Type: -

Identifier Source: secondary_id

Danish EthicalH-D-2008-060

Identifier Type: -

Identifier Source: secondary_id

Danish Datatilsyn2007-41-1652

Identifier Type: -

Identifier Source: secondary_id

JDRF file no. 17-2007-1804

Identifier Type: -

Identifier Source: secondary_id

2007-007146-34

Identifier Type: -

Identifier Source: org_study_id