Type 1 DiabetesPhase 2/3AIDANCT00711503
Anti-Interleukin-1 in Diabetes Action
A Phase 2/3 study testing anakinra and saline in people with Type 1 Diabetes, run by Steno Diabetes Center Copenhagen at 17 sites in 7 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- anakinra and saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 17 sitesin 7 countries
- Study dates
- Jan 2009to Jun 2012
- Phase
- Phase 2/3
- 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 18 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 13Show fewer
- 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.
Trial locations and contacts
17 sites in 7 countries.
17 sites in 7 countries
Denmark5 sites
Aalborg Hospital
Aalborg, 9100
Aarhus Universitetshospital
Aarhus, 8000 C
Bispebjerg Universitetshospital
Copenhagen, 2400 NV
Steno Diabetes Center
Gentofte Municipality, 2820
Nordsjællands Hospital, Hillerød
Hillerød, 3400
Germany4 sites
Leibniz Center for Diabetes research, Heinrich-Heine University
Düsseldorf, 40225
University of Frankfurt am Main
Frankfurt am Main, 60590
Institut für Diabetesforschung, Munich University of Technology
Munich, 80804
Ulm University, Dept. of Internal Medicine
Ulm, Donau, 89081
Spain4 sites
Hospital de Cruces, Diabetes Research Group
Barakaldo, Bizkaia, 48903
Hospital Santa Creu i Sant Pau
Barcelona, 08025
Hospital Unversitario Insular de Gran Canaria
Las Palmas, Gran Canaria, 35016
Hospital Arnua de Vilanova
Lleida, 25198
About this study
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
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.
Read the 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.
- Conditions
- Type 1 Diabetes
- Being tested
- anakinra, saline
- Keywords
- endogenous insulin production, C-peptide level, insulin requirement
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anakinraDrug
Also called Kineret
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
salineDrug
The patients are instructed to administer placebo (saline) once daily by subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| 2 | Placebo comparator | The patients are instructed to administer placebo by subcutaneous injection Receives: 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 Receives: Drug: anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Δ 2-h AUC C-peptide response
Measured: 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
Measured: 1 month, 3 months, 6 months, 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2008 (estimated)
- Study startJan 2009
- Primary completionJan 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, Oeresund Diabetes Academy
- Responsible party
- Principal investigator, Lise Tarnow, Steno Diabetes Center Copenhagen
- Investigators
- Thomas R Mandrup-Poulsen, MD, DMSc, Principal investigator, Steno Diabetes Center CopenhagenMarc Donath, Study director, Universtity of ZürichFlemming Pociot, DMSc, Study director, Steno Diabetes Center CopenhagenCharles Dinarello, Study director, University of Colorado Health Science CenterEdwin Gale, Professor, Study chair, Bristol University, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00711503
- Sponsor's protocol ID
- 2007-007146-34
- Other IDs
- EudraCT 2007-007146-34, Danish EthicalH-D-2008-060, Danish Datatilsyn2007-41-1652, JDRF file no. 17-2007-1804
- Acronym
- AIDA
- Status last verified
- Aug 2012
- First submitted
- 3 Jul 2008
- Last updated
- 3 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19405081Moran 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.
PubMed 23562090
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00711503
- Acronym / sponsor ID
- AIDA / 2007-007146-34
- Conditions
- Type 1 Diabetes
- Keywords
- endogenous insulin production, C-peptide level, insulin requirement
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, Oeresund Diabetes Academy
- Study start
- Jan 2009
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 9 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 | Placebo comparator | Drug: salineThe patients are instructed to administer placebo by subcutaneous injection |
| 1 | Experimental | Drug: anakinraThe 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 |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anakinraAlso: KineretThe 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 | 1 |
| salineThe patients are instructed to administer placebo (saline) once daily by subcutaneous injection | Drug | 2 |
Primary outcome
Δ 2-h AUC C-peptide response
Time frame: 1 month, 3 months, 6 months, 9 months
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2012.
- Background: PubMed 19405081Pickersgill 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.
- Derived from this study: PubMed 23562090Moran 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas R Mandrup-Poulsen, MD, DMSc principal investigator
Steno Diabetes Center Copenhagen
Marc Donath study director
Universtity of Zürich
Flemming Pociot, DMSc study director
Steno Diabetes Center Copenhagen
17 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing anakinra and saline in people with Type 1 Diabetes, run by Steno Diabetes Center Copenhagen at 17 sites in 7 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 5 inclusion and 13 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 3 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Denmark, Germany, Spain, Italy, Netherlands and 2 more countries. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Δ 2-h AUC C-peptide response (time frame: 1 month, 3 months, 6 months, 9 months). 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 NCT00711503, 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 3 Sep 2012.