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

NCT06570278 | Recruiting

• 2 other identifiers: C17-272021-A02597-34
• Study Type: interventional
• Target: 1,020
• Locations: 1 country
• Sites: 26

Brief Summary

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.

Conditions

Diabetes Mellitus

Keywords

Next generation sequencing genome; Diagnostic study; Medico-economic study

Outcome Measures

Primary Outcomes (1)

• Number of patients with one or several genetic alterations likely causal of diabetes

  Number of patients in each group with one or several genetic alterations likely causal of diabetes

  At 6 months in control group and 12 months in interventional group

Secondary Outcomes (28)

• Number of patients with an impact on treatment modification

  5 years

• Number of genetic alterations likely causal of diabetes

  At 6 months in control group and 12 months in interventional group

• Feasibility of the whole genome sequencing (WGS) coupled with multidisciplinary conciliation meeting (MCM) on diagnosis of atypical forms of diabetes: time to access to the genetic data

  At 6 months in control group and 12 months in interventional group

• Feasibility of the WGS coupled with MCM on diagnosis of atypical forms of diabetes: time between blood sampling and MCM

  At 6 months in control group and 12 months in interventional group

• Feasibility of the WGS coupled with MCM on diagnosis of atypical forms of diabetes: time between blood sampling and access to WGS report

  At 6 months in control group and 12 months in interventional group

Other Outcomes (5)

• Number and characteristics of new genomic variations responsible for diabetes development

  At 6 months in control group and 12 months in interventional group

• Number and characteristics of genomic variations and their association with defined phenotypes including integrated diagnostic biomarkers

  At 6 months in control group and 12 months in interventional group

• Number and characteristics of genomic variations known as drug targets

  At 6 months in control group and 12 months in interventional group

Study Arms (2)

control procedure

NO INTERVENTION

In-silico analysis of a panel of validated genes (ISApanel). Patients recruited along control procedure will stay in their arm using current genetic diagnosis practices and standard of care that may differ from one center to another

intervention procedure

EXPERIMENTAL

WGS coupled with MCM

Diagnostic Test: WGS coupled with MCM

Interventions

WGS coupled with MCM DIAGNOSTIC_TEST

Whole genome will be screened and analysis will focus on pathogenic and likely pathogenic variants. The list of variants of interest will be recorded until examination and discussion during the MCM. MCM will edit a final synthesis concerning the pathogenicity of identified variants.

intervention procedure

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Presenting atypical diabetes defined by at least one of the following:
• Exocrine pancreatic disease
• Familial history: diabetes diagnosed in a parent, child or sibling
• 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

You may not qualify if:

• 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)
• Patient who had a bone marrow transplant
• 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).

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• Rennes University Hospital: collaborator
• Commissariat A L'energie Atomique: collaborator
• Central Hospital, Nancy, France: collaborator
• Nantes University Hospital: collaborator
• APHP: collaborator
• Université Lumière Lyon 2: collaborator
• Hospices Civils de Lyon: collaborator
• Imagine Institute: collaborator
• University Hospital, Toulouse: collaborator

Study Sites (26)

University Hospital

Amiens, France

RECRUITING

University Hospital

Angers, France

RECRUITING

University Hospital Jean Minjoz

Besançon, France

RECRUITING

University Hospital Haut Lévêque

Bordeaux, France

RECRUITING

University Hospital Cavale Blanche

Brest, France

RECRUITING

Centre Hospitalier Sud Francilien

Corbeil-Essonnes, France

RECRUITING

University Hospital Bocage

Dijon, France

RECRUITING

University Hospital Michallon

Grenoble, France

RECRUITING

Assistance Publique Hôpitaux de Paris, Bicêtre Hospital

Le Kremlin-Bicêtre, France

NOT YET RECRUITING

University Hospital Louis Pradel

Lyon, France

RECRUITING

University Hospital Sud

Lyon, France

RECRUITING

University Hospital Conception

Marseille, France

RECRUITING

University Hospital Lapeyronie

Montpellier, France

RECRUITING

University Hospital

Nancy, France

NOT YET RECRUITING

University Hospital Laennec

Nantes, France

RECRUITING

University Hospital L'Archet

Nice, France

NOT YET RECRUITING

Assistance Publique Hôpitaux de Paris, Bichat - Claude Bernard Hospital

Paris, France

RECRUITING

Assistance Publique Hôpitaux de Paris, Cochin Hospital

Paris, France

RECRUITING

Assistance Publique Hôpitaux de Paris, Lariboisière Hospital

Paris, France

RECRUITING

Assistance Publique Hôpitaux de Paris, Saint Antoine Hospital

Paris, France

RECRUITING

Assistance Publique Hôpitaux de Paris- La Pitié Salpêtrière Hospital

Paris, France

RECRUITING

University Hospital

Poitiers, France

NOT YET RECRUITING

Rennes University Hospital

Rennes, France

RECRUITING

University Hospital Bois Guillaume

Rouen, France

RECRUITING

Strasbourg University Hospital

Strasbourg, France

RECRUITING

University Hospital Rangueil

Toulouse, France

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus; Disease

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jean-François GAUTIER

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean-François Gautier

CONTACT

+33 01 49 95 90 20; jean-francois.gautier@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: We plan to randomize one patient in the control group for two in the intervention group.

Study Record Dates

• First Submitted: February 2, 2024
• First Posted: August 26, 2024
• Study Start: October 30, 2024
• Primary Completion (Estimated): November 1, 2031
• Study Completion (Estimated): November 1, 2034
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

FR (26)