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

NCT ID: NCT03936634

Last Updated: 2020-12-21

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

UNKNOWN

Total Enrollment

6000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-11-14

Study Completion Date

2022-10-31

Brief Summary

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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.

Detailed Description

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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 4500 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.

Conditions

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Type 1 Diabetes Mellitus

Keywords

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Observation study First degree relatives Beta cell C-Peptide Immune cells Disease progression

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Newly Diagnosed (ND)

Recruited within 6 weeks of type 1 diabetes diagnosis. Age between 1 and \<45 years

No interventions assigned to this group

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

No interventions assigned to this group

Eligibility Criteria

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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.


* 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

* 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:


* 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.
Minimum Eligible Age

1 Year

Maximum Eligible Age

44 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Innovative Medicines Initiative

OTHER

Sponsor Role collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role collaborator

The Leona M. and Harry B. Helmsley Charitable Trust

OTHER

Sponsor Role collaborator

University of Cambridge

OTHER

Sponsor Role lead

Responsible Party

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David Dunger

Professor of Paediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David B Dunger

Role: PRINCIPAL_INVESTIGATOR

University of Cambridge

Mikael Knip

Role: PRINCIPAL_INVESTIGATOR

University of Helsinki

Chantal Mathieu

Role: STUDY_CHAIR

Katholieke Universteit Leuven

Locations

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Medical University of Graz

Graz, , Austria

Site Status RECRUITING

Universitee Libre de Bruxelles

Brussels, , Belgium

Site Status RECRUITING

Katholieke Universiteit Leuven

Leuven, , Belgium

Site Status RECRUITING

University of Copenhagen

Copenhagen, , Denmark

Site Status RECRUITING

University of Helsinki

Helsinki, , Finland

Site Status RECRUITING

University of Oulu

Oulu, , Finland

Site Status RECRUITING

Turku University Hospital

Turku, , Finland

Site Status NOT_YET_RECRUITING

Institut National de la Sante et de la Recherche Medicale (INSERM)

Paris, , France

Site Status RECRUITING

Children's Hospital Auf der Bult, Hannover Medical School

Hanover, , Germany

Site Status RECRUITING

University of Ulm

Ulm, , Germany

Site Status RECRUITING

San Raffaele Hospital

Milan, , Italy

Site Status NOT_YET_RECRUITING

Ospedale Pediatrico Bambino Gesu

Rome, , Italy

Site Status RECRUITING

University of Studi di Siena

Siena, , Italy

Site Status RECRUITING

University of Luxembourg

Luxembourg, , Luxembourg

Site Status RECRUITING

Oslo Universitetssytehus HF

Oslo, , Norway

Site Status RECRUITING

Medical University of Silesia Katowice

Katowice, , Poland

Site Status RECRUITING

University of Ljubljana

Ljubljana, , Slovenia

Site Status RECRUITING

University of Lund

Malmo, , Sweden

Site Status RECRUITING

University of Cambridge

Cambridge, , United Kingdom

Site Status RECRUITING

Countries

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Austria Belgium Denmark Finland France Germany Italy Luxembourg Norway Poland Slovenia Sweden United Kingdom

Central Contacts

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David B Dunger

Role: CONTACT

Phone: +44 1223 336886

Email: [email protected]

Sylvaine Bruggraber

Role: CONTACT

Phone: +44 1223 769063

Email: [email protected]

Facility Contacts

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Thomas Pieber

Role: primary

Gerlies Treiber

Role: backup

Miriam Cnop

Role: primary

Chantal Mathieu

Role: primary

Kristina Casteels

Role: backup

Jesper Johannesen

Role: primary

Recruitment queries

Role: primary

Riitta Veijola

Role: primary

Jorma Toppari

Role: primary

Recruitment queries

Role: primary

Recruitment queries

Role: primary

Reinhard Holl

Role: primary

Stefanie Lanzinger

Role: backup

Pauline Grogan

Role: primary

Valentina Pampanini

Role: primary

Francesco Dotta

Role: primary

Carine De Beaufort

Role: primary

Knut Dahl-Jørgensen

Role: primary

Przemyslawa Jarosz-Chobot

Role: primary

Darja Smigoc

Role: primary

Linda Ahlkinst

Role: primary

Recruitment queries

Role: primary

References

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Andellini M, Haleem S, Angelini M, Ritrovato M, Schiaffini R, Iadanza E, Pecchia L. Artificial intelligence for non-invasive glycaemic-events detection via ECG in a paediatric population: study protocol. Health Technol (Berl). 2023;13(1):145-154. doi: 10.1007/s12553-022-00719-x. Epub 2023 Jan 23.

Reference Type DERIVED
PMID: 36761922 (View on PubMed)

Wilhelm-Benartzi CS, Miller SE, Bruggraber S, Picton D, Wilson M, Gatley K, Chhabra A, Marcovecchio ML, Hendriks AEJ, Morobe H, Chmura PJ, Bond S, Aschemeier-Fuchs B, Knip M, Tree T, Overbergh L, Pall J, Arnaud O, Haller MJ, Nitsche A, Schulte AM, Mathieu C, Mander A, Dunger D. Study protocol: Minimum effective low dose: anti-human thymocyte globulin (MELD-ATG): phase II, dose ranging, efficacy study of antithymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes. BMJ Open. 2021 Dec 7;11(12):e053669. doi: 10.1136/bmjopen-2021-053669.

Reference Type DERIVED
PMID: 34876434 (View on PubMed)

Other Identifiers

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210497

Identifier Type: OTHER

Identifier Source: secondary_id

115797

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

INNODIA 01

Identifier Type: -

Identifier Source: org_study_id