Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT06570278 En recrutement IDF

Titre

Role of High-Throughput Whole Genome Sequencing for the Diagnosis and Care of Atypical Diabetes

Type

Interventional

Pathologie

Diabète

Phase

N/A

Promoteur

Institut National de la Santé Et de la Recherche Médicale, France (Voir sur ClinicalTrials)

Date de début

octobre 2024

Date de fin

novembre 2034

Dernière mise à jour

13 septembre 2025

Résumé

The main objective of the study is to assess the contribution of whole genome sequencing (WGS) coupled with a multidisciplinary conciliation meeting (MCM) on diagnosis of atypical forms of diabetes compared to an in-silico analysis of a panel of validated genes (ISApanel), corresponding to current practice, in a randomized trial. Notably, the questions it aims to answer are: - The feasibility of the WGS coupled with MCM on diagnosis of atypical forms of diabetes, - The contribution of WGS coupled with MCM on number of genetic alterations likely causal of diabetes identified and with a modification in care and support of patients. After inclusion and sampling for genotyping, patients will be followed for 5 years. The target population is 1020 adults with atypical diabetes for whom it is possible to obtain a blood sample.

Détail

Voir le détail The prevalence of diabetes is 7.4% in France among people aged 20 to 79 years in 2015. We must also consider "pre-diabetes" (subjects with glucose intolerance), whose prevalence is equivalent to that of diabetes (2012 estimate). The incidence of diabetes is exploding both for type 2 diabetes, which represents 85% of diabetes, and for type 1 diabetes, which represents 10% of cases and starts one out of two times before the age of 20. Diabetes typing is essential to guide therapeutic choices, particularly the use of insulin. This typing is based on the pathophysiology of the disease, distinguishing insulinopenia from autoimmune causes in type 1 diabetes, monogenic diabetes, secondary or atypical diabetes and type 2 diabetes, where insulinopenia and insulin resistance coexist. Thus, while a formal biological diagnosis is possible for some forms of atypical diabetes and for type 1 diabetes, no biological parameter is currently available for type 2 diabetes, which remains a diagnosis of exclusion. As a result, diabetes represents a source of diagnostic and therapeutic erraticism, amplified by the clinical heterogeneity of type 2 diabetes, which is obvious and underestimated, and by a clinical phenotyping of patients that is often defective. The economic consequences are important because the health costs are very different depending on whether or not patients are treated with insulin. Type 1 and type 2 diabetes are examples of chronic, non-transmissible, multigenic, multifactorial diseases. However, less than 10% of the heritability of type 2 diabetes is currently explained by the associated genetic variants. And although genetic tests exist to diagnose certain monogenic diabetes, this diagnosis is made in less than 20% of cases, mainly in the presence of an atypical clinical presentation of diabetes. Moreover, there is no reason to rule out the hypothesis of paucigenic forms, at the interface of monogenic diabetes and multigenic forms as usually envisaged, as has been observed in chronic pancreatitis, which is also accompanied by diabetes. The study will be conducted according to a randomized trial design comparing two diagnostic strategies defined as follows: - Control strategy: in silico analysis of a panel of validated genes (ISApanel - Diabetome 1). Patients recruited along the control procedure will stay in their group using current genetic diagnosis practices and standard of care that may differ from one center to another. - Intervention strategy: whole genome sequencing coupled with multidisciplinary conciliation meeting. We plan to randomize one patient in the control group for two in the intervention group. The main objective of the study is to assess the contribution of whole genome sequencing (WGS) coupled with a multidisciplinary conciliation meeting (MCM) on diagnosis of atypical forms of diabetes compared to an in-silico analysis of a panel of validated genes (ISApanel), corresponding to current practice. The target population is 1020 adults with atypical diabetes for whom it is possible to obtain a blood sample. Fermer le détail

Etablissements

Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
AP-HP - Hôpital Bichat	Louis POTIER	En recrutement IDF	Contact (sur clinicalTrials)
AP-HP - Hôpital Cochin	Danièle DUBOIS-LAFORGUE	En recrutement IDF	Contact (sur clinicalTrials)
AP-HP - Hôpital Saint Antoine	Camille VATIER	Recrutement non commencé	Contact (sur clinicalTrials)
CENTRE HOSPITALIER SUD FRANCILIEN	Coralie AMADOU	En recrutement IDF	Contact (sur clinicalTrials)
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
Assistance Publique Hôpitaux de Paris- La Pitié Salpêtrière Hospital - Paris - France	Cécile CIANGURA	Recrutement non commencé	Contact (sur clinicalTrials)
Assistance Publique Hôpitaux de Paris, Bicêtre Hospital - Le Kremlin-Bicêtre - France	Jacques YOUNG	Recrutement non commencé	Contact (sur clinicalTrials)
Assistance Publique Hôpitaux de Paris, Lariboisière Hospital - Paris - France	Jean-François GAUTIER	En recrutement	Contact (sur clinicalTrials)
Rennes University Hospital - Rennes - France	Agathe GUENEGO	En recrutement	Contact (sur clinicalTrials)
Strasbourg University Hospital - Strasbourg - France	Luc RAKOTOARISOA	En recrutement	Contact (sur clinicalTrials)
University Hospital - Amiens - France	Abdallah AL SALAMEH	En recrutement	Contact (sur clinicalTrials)
University Hospital - Angers - France	Ingrid ALLIX	En recrutement	Contact (sur clinicalTrials)
University Hospital - Nancy - France	Bruno GUERCI	Recrutement non commencé	Contact (sur clinicalTrials)
University Hospital - Poitiers - France	Héléna MOSBAH	Recrutement non commencé	Contact (sur clinicalTrials)
University Hospital Bocage - Dijon - France	Bruno VERGES	En recrutement	Contact (sur clinicalTrials)
University Hospital Bois Guillaume - Rouen - France	Gaetan PREVOST	En recrutement	Contact (sur clinicalTrials)
University Hospital Cavale Blanche - Brest - France	Philippe THUILLIER	En recrutement	Contact (sur clinicalTrials)
University Hospital Conception - Marseille - France	Patrice DARMON	En recrutement	Contact (sur clinicalTrials)
University Hospital Haut Lévêque - Bordeaux - France	Vincent RIGALLEAU	Recrutement non commencé	Contact (sur clinicalTrials)
University Hospital Jean Minjoz - Besançon - France	Sophie BOROT	En recrutement	Contact (sur clinicalTrials)
University Hospital Laennec - Nantes - France	Samy HADJADJ	En recrutement	Contact (sur clinicalTrials)
University Hospital Lapeyronie - Montpellier - France	Ariane SULTAN	En recrutement	Contact (sur clinicalTrials)
University Hospital L'Archet - Nice - France	Nicolas CHEVALIER	Recrutement non commencé	Contact (sur clinicalTrials)
University Hospital Louis Pradel - Lyon - France	Sybil CHARRIERE	En recrutement	Contact (sur clinicalTrials)
University Hospital Michallon - Grenoble - France	Sandrine LABLANCHE	Recrutement non commencé	Contact (sur clinicalTrials)
University Hospital Rangueil - Toulouse - France	Pierre GOURDY	En recrutement	Contact (sur clinicalTrials)
University Hospital Sud - Lyon - France	Emmanuel DISSE	En recrutement	Contact (sur clinicalTrials)

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

Inclusion Criteria:

- Subjects ≥18 years with confirmed diabetes mellitus according to WHO criteria (World
Health Organization: Definition and diagnosis of diabetes mellitus and intermediate
hyperglycemia: Report of a WHO/IDF Consultation. Geneva, World Health Org., 2006.)

- Age ≤ 45 years at diabetes diagnosis

- Body mass index ≤ 35 kg/m² at diabetes diagnosis

- Negative results of specific antibodies determination (GAD65, IA2, ZnT8) until the
inclusion visit

- Presenting atypical diabetes defined by at least one of the following:

- Exocrine pancreatic disease

- Familial history: diabetes diagnosed in first degree relatives from at least 2
generations

- Notion of familial consanguinity

- Syndromic clinical features (dysmorphy, developmental delay, mental retardation...)
or unusual abnormalities/features that are not part of diabetic complications or
co-morbidities;

- Early occurrence of microvascular complications (≤ 5 years after diabetes diagnosis)

- Major insulinopenia at diagnosis (C peptide <0.2 nmol/L and/or documented
ketosis)

- Patient who conserved endogenous insulin secretion (positive C peptide value) but a
need for insulin therapy initiation during the first year following diagnosis due to
therapeutic failure of well conducted therapeutic intensification

- Stated willingness to comply with all study procedures and availability for the
duration of the study

- Patient with a social security number in compliance with the French law
(dispositions relatives aux recherches impliquant la personne humaine prévues aux
articles L 1121-1 et suivants du Code de la Santé Publique)

- Signed and dated informed consent form

Critère de non inclusion

- Pregnant or breastfeeding woman,

- Any contraindication to the study exams including known allergies or
contraindication to contrasts for the scan

- Patient with known monogenic diabetes (defined as identification of class 4 and 5
variants according to ACMG)

- First or second-degree relatives with monogenic diabetes established by molecular
genetics (class 4 and 5 variants according to ACMG)

- Patient with known secondary diabetes (i.e. endocrine disorders such as Cushing
syndrome, pancreatectomy, drug-induced diabetes)

- Any condition which in the Investigator's opinion makes it undesirable for the
subject to participate in the trial or which would jeopardize compliance with the
protocol,

- Individuals under legal protection (sauvegarde de justice).

NCT06570278 - Role of High-Throughput Whole Genome Sequencing for the Diagnosis and Care of Atypical Diabetes

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