Role of High-Throughput Whole Genome Sequencing for the Diagnosis and Care of Atypical Diabetes
NCT Number: NCT06570278
Acronym: GLUCOGEN
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Diabetes Mellitus
Interventions: DIAGNOSTIC_TEST: WGS coupled with MCM
Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Collaborators: Commissariat A L'energie Atomique|Rennes University Hospital|Central Hospital, Nancy, France|Nantes University Hospital|Imagine Institute
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 1020
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: DIAGNOSTIC
Start Date: 2024-09
Completion Date: 2034-11
Locations: University Hospital, Amiens, France|University Hospital, Angers, France|University Hospital Jean Minjoz, Besançon, France|University Hospital Haut Lévêque, Bordeaux, France|University Hospital Cavale Blanche, Brest, France|Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France|University Hospital Bocage, Dijon, France|University Hospital Michallon, Grenoble, France|Assistance Publique Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France|University Hospital Louis Pradel, Lyon, France|University Hospital Sud, Lyon, France|University Hospital Conception, Marseille, France|University Hospital Lapeyronie, Montpellier, France|University Hospital, Nancy, France|University Hospital Laennec, Nantes, France|University Hospital L'Archet, Nice, France|Assistance Publique Hôpitaux de Paris, Bichat - Claude Bernard Hospital, Paris, France|Assistance Publique Hôpitaux de Paris, Cochin Hospital, Paris, France|Assistance Publique Hôpitaux de Paris, Lariboisière Hospital, Paris, France|Assistance Publique Hôpitaux de Paris, Saint Antoine Hospital, Paris, France|Assistance Publique Hôpitaux de Paris- La Pitié Salpêtrière Hospital, Paris, France|University Hospital, Poitiers, France|Rennes University Hospital, Rennes, France|University Hospital Bois Guillaume, Rouen, France|Strasbourg University Hospital, Strasbourg, France|University Hospital Rangueil, Toulouse, France

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.

Primary Outcome Measures: 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 Outcome Measures: Number of patients with an impact on treatment modification, Number of patients in each group with an impact on treatment modification including discontinuation and reason of this modification, 5 years|Number of genetic alterations likely causal of diabetes, Number of genetic alterations likely causal of diabetes (classified as class 4 or 5 variants), 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, time between blood sampling and availability of genetic data by GLUCOGEN laboratories, 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, 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, time between blood sampling and access to WGS report produced by GLUCOGEN laboratory, 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 date of the WGS result visit, time between blood sampling and date of the WGS result visit, 5 years|Genotype-Insulin secretion phenotype association, Genotype-phenotype associations corresponding to insulin secretion, At 6 months in control group and 12 months in interventional group|Genotype-Insulin sensitivity phenotype association, Genotype-phenotype associations corresponding to insulin sensitivity

• Body composition, At 6 months in control group and 12 months in interventional group|Genotype-body composition phenotype association, Genotype-phenotype associations corresponding to body composition, At 6 months in control group and 12 months in interventional group|Glycemic control without insulin treatment, Percentage of patients with glycated hemoglobin (HbA1c) target below 7% without insulin treatment at 2, 3, 4 and 5 years, 5 years|Glycemic control without severe hypoglycemia, Percentage of patients with glycated hemoglobin (HbA1c) target below 7% without severe hypoglycemia in the last 6 months and with a change in body mass index \< 1 kg/m² in the last 6 months at 2, 3, 4 and 5 years, 5 years|Number of long-term micro and macro vascular complications associated with diabetes and time to occurrence of the first complication, Number of long-term micro and macro vascular complications associated with diabetes and time to occurrence of the first complication:

* Retinopathy
* Nephropathy
* Neuropathy
* Cardiovascular disease
* Liver disease, 5 years|Patient-Reported Outcomes (PROs), evaluated with SF36 questionnaire, SF36 questionnaire at baseline, every 6 months during the first 2 years, then every year until 5 years., 5 years|Patient-Reported Outcomes (PROs), evaluated with Euroquol Dimension (EQ-5D-5L) questionnaire, EQ-5D-5L questionnaire at baseline, every 6 months during the first 2 years, then every year until 5 years.

• ADDQOL questionnaire, 5 years|Patient-Reported Outcomes (PROs), evaluated with Audit of Diabetes Dependent Quality of Life (ADDQOL) questionnaire, ADDQOL questionnaire at baseline, every 6 months during the first 2 years, then every year until 5 years., 5 years|Number of participants agreeing to have access to secondary findings (SF), Number of participants agreeing to have access to secondary findings (SF), At 6 months in control group and 12 months in interventional group|Number and type of SFs (class 4 or 5 variant(s)) identified in participants that specifically consent to have access to SF, Number and type of SFs (class 4 or 5 variant(s)) identified in participants that specifically consent to have access to SF, At 6 months in control group and 12 months in interventional group|Percentage of SFs in the studied population, Percentage of SFs in the studied population, At 6 months in control group and 12 months in interventional group|Number and type of medical consequences following identification of SFs, Number and type of medical consequences following identification of SFs, 5 years|Direct costs associated with current diagnosis practices (ISApanel), Direct costs associated with current diagnosis practices (ISApanel), 5 years|Direct costs associated with WGS coupled with MCM, Direct costs associated with WGS coupled with MCM, 5 years|Incremental cost-effectiveness ratio of WGS coupled with MCM compared to current diagnosis practices (ISApanel), Incremental cost-effectiveness ratio of WGS coupled with MCM compared to current diagnosis practices (ISApanel), 5 years|Incremental cost-utility ratio of WGS coupled with MCM compared to current diagnosis practices (ISApanel), Incremental cost-utility ratio of WGS coupled with MCM compared to current diagnosis practices (ISApanel), 5 years|Cost-benefit of WGS coupled with MCM compared to current diagnosis practices, Cost-benefit of WGS coupled with MCM compared to current diagnosis practices (ISApanel) in terms of cost of wandering diagnosis and care procedure avoided, 5 years|Psychosocial issues related to genetic testing for atypical diabetes, Qualitative data related to patients' expectations regarding genetic testing related to atypical diabetes and needs to receive SF information., At 6 months in control group and 12 months in interventional group|Psychosocial issues related to genetic testing for atypical diabetes, * Qualitative data (discourse - semi-structured individual interviews) related to patients experience following genetic testing results for atypical diabetes
* Qualitative data (discourse - semi-structured individual interviews) related to patients' experience of the GLUCOGEN trial, 5 years|Psychosocial issues related to patients' experience of the GLUCOGEN trial, Quantitative data (questionnaire), 18 months|Psychosocial issues related to professional's experience of the GLUCOGEN research protocol, Qualitative data (observation), including information regarding doctor-patient relationship and decision-making processes., 12 months
Other Outcome Measures: Number and characteristics of new genomic variations responsible for diabetes development, 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, 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, Number and characteristics of genomic variations known as drug targets, At 6 months in control group and 12 months in interventional group|Number and characteristics of genomic variations of metabolism, transport or drug targets of diabetes and their consequences on treatment response, Number and characteristics of genomic variations of metabolism, transport or drug targets of diabetes and their consequences on treatment response, At 6 months in control group and 12 months in interventional group|Number and characteristics of molecular targets in atypical diabetes, Number and characteristics of molecular targets in atypical diabetes, At 6 months in control group and 12 months in interventional group