Anti-Interleukin-1 in Diabetes Action (AIDA)

This study has been completed.
Sponsor:
Collaborators:
Juvenile Diabetes Research Foundation
Oeresund Diabetes Academy
Information provided by (Responsible Party):
Lise Tarnow, Steno Diabetes Center
ClinicalTrials.gov Identifier:
NCT00711503
First received: July 3, 2008
Last updated: August 31, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes
Drug: anakinra
Drug: saline
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised Clinical Trial of the Effect of Interleukin-1 Receptor Antagonism on the Insulin Production in Patients With New Onset Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Steno Diabetes Center:

Primary Outcome Measures:
  • Δ 2-h AUC C-peptide response [ Time Frame: 1 month, 3 months, 6 months, 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 1 month, 3 months, 6 months, 9 months ] [ Designated as safety issue: No ]

Enrollment: 69
Study Start Date: January 2009
Study Completion Date: June 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 2
The patients are instructed to administer placebo by subcutaneous injection
Drug: saline
The patients are instructed to administer placebo (saline) once daily by subcutaneous injection
Other Name: saline
Experimental: 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
Drug: 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
Other Name: Kineret

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00711503

Locations
Denmark
Aalborg Hospital
Aalborg, Denmark, 9100
Aarhus Universitetshospital
Aarhus, Denmark, 8000 C
Bispebjerg Universitetshospital
Copenhagen, Denmark, 2400 NV
Steno Diabetes Center
Gentofte, Denmark, 2820
Nordsjællands Hospital, Hillerød
Hillerød, Denmark, 3400
Germany
Ulm University, Dept. of Internal Medicine
Ulm, Donau, Germany, 89081
Leibniz Center for Diabetes research, Heinrich-Heine University
Duesseldorf, Germany, 40225
University of Frankfurt am Main
Frankfurt am Main, Germany, 60590
Institut für Diabetesforschung, Munich University of Technology
Munich, Germany, 80804
Italy
University Campus Bio-Medico
Rome, Italy, 00128
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2300 RC
Poland
Medical University of Bialystok
Bialystok, Poland, 15-269
Spain
Hospital de Cruces, Diabetes Research Group
Barakaldo, Bizkaia, Spain, 48903
Hospital Unversitario Insular de Gran Canaria
Las Palmas, Gran Canaria, Spain, 35016
Hospital Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital Arnua de Vilanova
Lleida, Spain, 25198
Switzerland
University Hospital Zürich
Zürich, Switzerland, CH-8091
Sponsors and Collaborators
Steno Diabetes Center
Juvenile Diabetes Research Foundation
Oeresund Diabetes Academy
Investigators
Principal Investigator: Thomas R Mandrup-Poulsen, MD, DMSc Steno Diabetes Center
Study Director: Marc Donath Universtity of Zürich
Study Director: Flemming Pociot, DMSc Steno Diabetes Center
Study Director: Charles Dinarello University of Colorado Health Science Center
Study Chair: Edwin Gale, Professor Bristol University, UK
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Lise Tarnow, professor, Steno Diabetes Center
ClinicalTrials.gov Identifier: NCT00711503     History of Changes
Other Study ID Numbers: 2007-007146-34, EudraCT 2007-007146-34, Danish EthicalH-D-2008-060, Danish Datatilsyn2007-41-1652, JDRF file no. 17-2007-1804
Study First Received: July 3, 2008
Last Updated: August 31, 2012
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee

Keywords provided by Steno Diabetes Center:
endogenous insulin production
C-peptide level
insulin requirement

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014