Anti-Interleukin-1 in Diabetes Action

NCT00711503 | Completed Phase 2 DMC

• 5 other identifiers: 2007-007146-34EudraCT 2007-007146-34Danish EthicalH-D-2008-060Danish Datatilsyn2007-41-1652JDRF file no. 17-2007-1804
• Study Type: interventional
• Target: 69
• Locations: 7 countries
• Sites: 17

Brief Summary

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.

Conditions

Type 1 Diabetes

Keywords

endogenous insulin production; C-peptide level; insulin requirement

Outcome Measures

Primary Outcomes (1)

• Δ 2-h AUC C-peptide response

  1 month, 3 months, 6 months, 9 months

Secondary Outcomes (1)

• Incremental and/or peak C-peptide response, Time to peak C-peptide, insulin requirement per kg body weight per day,frequency of insulin free state with maintenance of HbA1c <7.5%, HbA1c, Means of fasting glucose values, circulating IL-6 and CRP

  1 month, 3 months, 6 months, 9 months

Study Arms (2)

2

PLACEBO COMPARATOR

The patients are instructed to administer placebo by subcutaneous injection

Drug: saline

1

EXPERIMENTAL

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

Drug: anakinra

Interventions

anakinra 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

Also known as: Kineret

1

saline DRUG

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

2

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• Juvenile Diabetes Research Foundation: collaborator
• Oeresund Diabetes Academy: collaborator

Study Sites (17)

Aalborg Hospital

Aalborg, 9100, Denmark

Location

Aarhus Universitetshospital

Aarhus, 8000 C, Denmark

Location

Bispebjerg Universitetshospital

Copenhagen, 2400 NV, Denmark

Location

Steno Diabetes Center

Gentofte Municipality, 2820, Denmark

Location

Nordsjællands Hospital, Hillerød

Hillerød, 3400, Denmark

Location

Ulm University, Dept. of Internal Medicine

Ulm, Donau, 89081, Germany

Location

Leibniz Center for Diabetes research, Heinrich-Heine University

Düsseldorf, 40225, Germany

Location

University of Frankfurt am Main

Frankfurt am Main, 60590, Germany

Location

Institut für Diabetesforschung, Munich University of Technology

Munich, 80804, Germany

Location

University Campus Bio-Medico

Rome, 00128, Italy

Location

Leiden University Medical Center

Leiden, 2300 RC, Netherlands

Location

Medical University of Bialystok

Bialystok, 15-269, Poland

Location

Hospital de Cruces, Diabetes Research Group

Barakaldo, Bizkaia, 48903, Spain

Location

Hospital Unversitario Insular de Gran Canaria

Las Palmas, Gran Canaria, 35016, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Arnua de Vilanova

Lleida, 25198, Spain

Location

University Hospital Zürich

Zurich, CH-8091, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 19405081 BACKGROUND

• 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.

  PMID: 23562090 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Interleukin 1 Receptor Antagonist Protein; Sodium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Thomas R Mandrup-Poulsen, MD, DMSc

  Steno Diabetes Center Copenhagen

  PRINCIPAL INVESTIGATOR

• Marc Donath

  Universtity of Zürich

  STUDY DIRECTOR

• Flemming Pociot, DMSc

  Steno Diabetes Center Copenhagen

  STUDY DIRECTOR

• Charles Dinarello

  University of Colorado Health Science Center

  STUDY DIRECTOR

• Edwin Gale, Professor

  Bristol University, UK

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: July 3, 2008
• First Posted: July 9, 2008
• Study Start: January 1, 2009
• Primary Completion: January 1, 2012
• Study Completion: June 1, 2012
• Last Updated: September 3, 2012

Record last verified: 2012-08

Locations

DE (4); CH (1); IT (1); ES (4); PL (1); NL (1); DK (5)