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An Innovative Approach Towards Understanding and Arresting Type 1 Diabetes (INNODIA) (INNODIA)

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ClinicalTrials.gov Identifier: NCT03936634
Recruitment Status : Recruiting
First Posted : May 3, 2019
Last Update Posted : May 10, 2019
Sponsor:
Collaborators:
Innovative Medicines Initiative
Juvenile Diabetes Research Foundation
The Leona M. and Harry B. Helmsley Charitable Trust
Information provided by (Responsible Party):
David Dunger, University of Cambridge

Brief Summary:

INNODIA is a global consortium linking 26 academic institutions, 4 industrial partners, a small to medium enterprise (SME), and 2 patient organisations, bringing their knowledge and experience together with one common goal: "To fight type 1 diabetes". (www.innodia.eu).

The project, approved in November 2015 and launched in January 2016, runs under the framework of the Innovative Medicines Initiative - Joint Undertaking (https://www.imi.europa.eu/projects-results/project-factsheets/innodia) with a dedicated governance structure ensuring close interaction, communication and adherence to the objectives and deliverables of the consortium.

The overall aim of INNODIA is to advance in a decisive way how to predict, stage, evaluate and prevent the onset and progression of type 1 diabetes (T1D). For this, INNODIA has established a comprehensive and interdisciplinary network of clinical and basic scientists, who are leading experts in the field of T1D research in Europe, with complementary expertise from the areas of immunology, Beta-cell biology, biomarker research and T1D therapy, joining forces in a coordinated fashion with industry partners and two foundations, as well as with all major stakeholders in the process, including regulatory bodies and patients with T1D and their families.

One of the objectives of INNODIA is to develop a new European clinical research network with standardized protocol based on repeated measures of C-peptide (including home measurements) and comprehensive collection of appropriate biological samples for 'omics', immune, viral and microbiome studies in new onset T1D patients and high-risk auto-antibody positive subjects. A protocol for the harmonization of sample collections in newly diagnosed type 1 diabetic patients and first degree relatives of patients with type 1 diabetes was developed following extensive preliminary work involving partners from across all specialities. Core laboratories with experience in their respective field were set up for analysis of auto-antibodies, fresh immune cells, handling of frozen immune cells, C-peptide measures. A series of standard operating procedures for sample collections and analysis were agreed. Sample tracking between clinical centres and central laboratories was included into a purposely designed electronic case report form (eCRF) into which all clinical and laboratory data collected are captured.


Condition or disease
Type 1 Diabetes Mellitus

Detailed Description:

This is a longitudinal observational study of the relationship between measures of β-cell function, genotype, immunological phenotype and potential environmental factors over time, in individuals with new onset T1D or first degree relatives at higher risk for T1D due to the presence of auto-antibodies.

It is a multicentre international study involving clinical centres across Europe which is unique in the following ways:

  1. The first such collaboration in Europe
  2. Novel evaluation of C-peptide/β-cell function using both home dried blood spots and regular hospital mixed meal tolerance tests or oral glucose tolerance tests
  3. Identical study procedures across all clinical centres
  4. Centralised analysis/storage of clinically relevant samples
  5. The creation of a living 'Biobank' whereby participants can be recalled for study on the basis of specific genotype/phenotypes
  6. Linkage to innovative study of novel biomarkers to inform future interventional strategies
  7. A potential pipeline for future recruitment and consent to novel innovative interventional strategies

The study is divided into 2 arms:

In arm A, the investigators plan to recruit 1500 newly diagnosed T1D patients within 6 weeks from diagnosis. The last study visit will be planned 2 years from diagnosis or until the end of the study. Therefore, the duration of the study will be approximately 2 years consisting of 5 visits. At baseline, C-peptide and immunophenotyping are evaluated. Follow up consists of regular mixed meal tolerance test (MMTT) and providing blood, urine and stool samples for 'omics', immune, viral and microbiome studies. Home dried blood spots (DBS) pre and post a standardized meal will be collected monthly for the duration of the study.

These recruited participants will be included for further observational study, confirmation of potential biomarkers and will ultimately provide a pipeline for future recruitment to interventional studies.

In arm B, the investigators plan to screen approximately 3000 unaffected first degree family members across all centres during the first 3 years. The family members will be screened for 4 auto-antibodies (GAD65, IA-2A, IAA, ZnT8A).

Unaffected family members who are auto-antibody positive will be followed up for approximately 4 years consisting of visits every 6 months for the first 2 years and then every 12 months until the end of the study. Follow up will consist of regular oral glucose tolerance test (OGTT) and providing blood, urine and stool samples for 'omics', immune, viral and microbiome studies. Home dried blood spots (DBS) will be collected monthly for the duration of the study.

Unaffected participants who are auto-antibody negative will be sent annual questionnaires until the end of the study.

All study participants will be consented to a living 'Biobank' where we will be able to request participants to be recalled by genotype/phenotype for further studies involving blood, urine and stool samples.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 4500 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: An Innovative Approach Towards Understanding and Arresting Type 1 Diabetes (INNODIA)
Actual Study Start Date : November 14, 2016
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : October 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Group/Cohort
Newly Diagnosed (ND)
Recruited within 6 weeks of type 1 diabetes diagnosis. Age between 1 and <45 years
Unaffected Family members (UFM)

Participants who are not diabetic but have a first degree relative with type 1 diabetes diagnosed < 45 years of age.

Age between 1 and <45 years




Primary Outcome Measures :
  1. Arm A - Newly Diagnosed people with Type 1 diabetes [ Time Frame: 24 months ]
    Rate of decline in Beta cell function as assessed by mixed meal tolerance test and home dried blood spot C-peptide measures over the first 24 months from diagnosis of Type 1 diabetes.

  2. Arm B - Auto-antibody positive first degree family members [ Time Frame: 48 months ]
    Development of diabetes as defined by the American Diabetes Association in auto-antibody positive family members followed longitudinally.


Secondary Outcome Measures :
  1. Arm A - Newly diagnosed patients with Type 1 diabetes [ Time Frame: 24 months ]
    Changes in HbA1c, insulin dose, autoantibody levels over the first 24 months from diagnosis.

  2. Arm A - Newly diagnosed patients with Type 1 diabetes - Systematic evaluation of biological samples [ Time Frame: 24 months ]
    Systematic evaluation of biological samples using multiple 'omics' approach to identify biomarkers which predict rate of deterioration in C-peptide measures

  3. Arm A - Newly diagnosed patients with Type 1 diabetes - Framework [ Time Frame: 24 months ]
    To develop a robust observational framework for future interventional studies.

  4. Arm B - Auto-antibody positive first degree family members - glucose tolerance [ Time Frame: 48 months ]
    Changes in glucose tolerance as determined by repeated oral glucose tolerance tests over the follow up period of 48 months

  5. Arm B - Auto-antibody positive first degree family members - Systematic evaluation of biological samples [ Time Frame: 48 months ]
    Systematic evaluation of biological samples, using multiple 'omics' approach, auto antibodies to identify biomarkers which predict rate of progression to diabetes.

  6. Arm B - Auto-antibody positive first degree family members - Framework [ Time Frame: 48 months ]
    Developing a robust framework for future interventional studies.


Biospecimen Retention:   Samples With DNA
Serum, plasma, whole blood, urine, stool, dried blood spot


Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 44 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Newly diagnosed patients with Type 1 diabetes.

Unaffected first degree family members of patients with type 1 diabetes.

Criteria

Newly diagnosed:

Inclusion Criteria:

  • Have given written informed consent to participate.
  • Be aged between 1 year and <45 years.
  • Less than 6 weeks from diagnosis of type 1 diabetes and requiring insulin treatment.

Exclusion Criteria:

  • Non-type 1 diabetes (type 2, monogenic diabetes and secondary diabetes)
  • Concurrent use of long term immunosuppressive agents including oral steroids or medication likely to confound the interpretation of study results.
  • Expected non-compliance with the protocol.
  • Any medical history or clinical relevant abnormality that is deemed by the principal investigator and/or co-investigator to make the patient ineligible for inclusion because problems in interpreting data or safety concern.
  • Participating in interventional or other drug research studies which could affect the primary objectives of the study.

Unaffected Family Members:

Inclusion Criteria:

  • Have given written informed consent to participate.
  • Be aged between 1 year and <45 years.
  • Have a first degree relative with type 1 diabetes (parent, child, full or half siblings) diagnosed <45 years of age

Exclusion Criteria:

  • The affected first degree relative has type 2 diabetes, monogenic diabetes or diabetes secondary to another medical condition.
  • Concurrent use of long term immunosuppressive agents including oral steroids or medication likely to confound the interpretation of study results.
  • Expected non-compliance with the protocol.
  • Any medical history or clinical relevant abnormality that is deemed by the principal investigator and/or co-investigator to make the patient ineligible for inclusion because problems in interpreting data or safety concern.
  • Participating in interventional or other drug research studies which could affect the primary objectives of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03936634


Contacts
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Contact: David B Dunger +44 1223 336886 dbd25@cam.ac.uk
Contact: Sylvaine Bruggraber +44 1223 769063 sb2194@medschl.cam.ac.uk

Locations
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Austria
Medical University of Graz Recruiting
Graz, Austria
Contact: Thomas Pieber       thomas.pieber@medunigraz.at   
Contact: Gerlies Treiber       gerlies.treiber@medunigraz.at   
Principal Investigator: Thomas Pieber         
Belgium
Universitee Libre de Bruxelles Recruiting
Brussels, Belgium
Contact: Miriam Cnop       mcnop@ulb.ac.uk   
Principal Investigator: Miriam Cnop         
Katholieke Universiteit Leuven Recruiting
Leuven, Belgium
Contact: Chantal Mathieu       chantal.mathieu@kuleuven.be   
Contact: Kristina Casteels       kristina.casteels@kuleuven.be   
Principal Investigator: Chantal Mathieu         
Sub-Investigator: Pieter Gillard         
Sub-Investigator: Kristina Casteels         
Denmark
University of Copenhagen Recruiting
Copenhagen, Denmark
Contact: Jesper Johannesen       jesper.johannesen@regionh.dk   
Principal Investigator: Jesper Johannesen         
Sub-Investigator: Jannet Svensson         
Finland
University of Helsinki Recruiting
Helsinki, Finland
Contact: Recruitment queries       pedia-innodia@helsinki.fi   
Principal Investigator: Mikael Knip         
University of Oulu Recruiting
Oulu, Finland
Contact: Riitta Veijola       riitta.veijola@oulu.fi   
Principal Investigator: Riitta Veijola         
France
Institut National de la Sante et de la Recherche Medicale (INSERM) Recruiting
Paris, France
Contact: Recruitment queries       trakrstudy@gmail.com   
Principal Investigator: Roberto Mallone         
Germany
Children's Hospital Auf der Bult, Hannover Medical School Recruiting
Hanover, Germany
Contact: Recruitment queries       innodia@hka.de   
Principal Investigator: Thomas Danne         
University of Ulm Recruiting
Ulm, Germany
Contact: Reinhard Holl       reinhard.holl@uni-ulm.de   
Contact: Stefanie Lanzinger       stefanie.lanzinger@uni-ulm.de   
Principal Investigator: Reinhard Holl         
Italy
University of Studi di Siena Recruiting
Siena, Italy
Contact: Francesco Dotta       francesco.dotta@unisi.it   
Principal Investigator: Francesco Dotta         
Luxembourg
University of Luxembourg Recruiting
Luxembourg, Luxembourg
Contact: Carine De Beaufort       debeaufort.carine@chl.lu   
Principal Investigator: Carine De Beaufort         
Norway
Oslo Universitetssytehus HF Recruiting
Oslo, Norway
Contact: Knut Dahl-Jørgensen       knut.dahl-jorgensen@medisin.uio.no   
Principal Investigator: Knut Dahl-Jørgensen         
Poland
Medical University of Silesia Katowice Recruiting
Katowice, Poland
Contact: Przemyslawa Jarosz-Chobot       przemka1@o2.pl   
Principal Investigator: Przemyslawa Jarosz-Chobot         
Slovenia
University of Ljubljana Recruiting
Ljubljana, Slovenia
Contact: Darja Smigoc       darja.smigoc@kclj.si   
Principal Investigator: Tadej Battelino         
United Kingdom
University of Cambridge Recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Recruitment queries       INNODIA-recruit@paed.cam.ac.uk   
Principal Investigator: Carlo Acerini         
Sponsors and Collaborators
University of Cambridge
Innovative Medicines Initiative
Juvenile Diabetes Research Foundation
The Leona M. and Harry B. Helmsley Charitable Trust
Investigators
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Principal Investigator: David B Dunger University of Cambridge
Principal Investigator: Mikael Knip Helsinki University
Study Chair: Chantal Mathieu Katholieke Universteit Leuven

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Responsible Party: David Dunger, Professor of Paediatrics, University of Cambridge
ClinicalTrials.gov Identifier: NCT03936634     History of Changes
Other Study ID Numbers: INNODIA 01
210497 ( Other Identifier: IRAS Project ID )
115797 ( Other Grant/Funding Number: Innovative Medicines Initiative )
First Posted: May 3, 2019    Key Record Dates
Last Update Posted: May 10, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by David Dunger, University of Cambridge:
Observation study
First degree relatives
Beta cell
C-Peptide
Immune cells
Disease progression

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases