Screening for Genetic Forms of Diabetes in Convention of Care for Children and Adolescents With Diabetes (GENEPEDIAB)

NCT04021199 | Completed

• 1 other identifier: GENEPEDIAB
• Study Type: interventional
• Target: 446
• Locations: 1 country
• Sites: 1

Brief Summary

Background/Aims: Diabetes, which affects 420 million people worldwide with a continuously rising incidence, is defined by a state of chronic hyperglycemia; a criterion referring to a heterogeneous group of diseases with various etiologies and distinct therapeutic options. Besides the two main forms of diabetes (i.e., type 1 (T1D) and type 2 (T2D)), there are rare subtypes of the disease called monogenic diabetes (or formerly MODY) that are hardly diagnosed because of their resemblance to T1D or T2D. Since these monogenic diabetes may appear early in life, a consortium of expert pediatric clinical centers was created under a clinical research initiative (the GENEPEDIAB study) to develop tools for accurate diagnosis of rare diabetes and to propose appropriate care to these children and adolescents wrongly assigned to T1D or T2D cohorts. The GENEPEDIAB study was initiated in the context of a broader collaborative project (DiaType) with the objective to develop personalized diabetes medicine and better patient care. Methods: For discrimination of patients with monogenic diabetes from those with classical forms of diabetes using the MODY probability calculator, patients enrolled in the GENEPEDIAB study are phenotyped and genotyped for T1D risk (anti-islet antibodies and HLA). Patients fulfilling sufficient criteria are then genotyped using the routine MODY panel, before being proposed a thorough gene analysis. More comprehensive genetic tests will be conducted in patients without anomalies found after the MODY gene-sequencing test. Perspective: the GENEPEDIAB study will enable the investigators to adapt treatment to diabetes etiology and help to provide genetic counseling to patients and their family members. The investigators anticipate that its broad genetic analyses will provide them with important information about the genetic susceptibility of these subgroups of patients with atypical diabetes.

Conditions

Diabetes Mellitus; MODY

Outcome Measures

Primary Outcomes (11)

• Diagnostic of atypical diabetes using follow-up of clinical parameters: Weight

  Weight in kilograms (Kg)

  At diabetes diagnosis

• Diagnostic of atypical diabetes using follow-up of clinical parameters: Height

  Height in meters (m)

  At diabetes diagnosis

• Diagnostic of atypical diabetes using follow-up of clinical parameters: BMI

  Body Mass Index (Kg/m²)

  At diabetes diagnosis

• Diagnostic of atypical diabetes using follow-up of laboratory results: HbA1c (%)

  Glicated hemoglobin (%)

  from diabetes diagnosis to study inclusion. (The study inclusion will be from 18 months after diagnosis to several years)

• Diagnostic of atypical diabetes using follow-up of laboratory results: HbA1c (mmol/mol)

  Glicated hemoglobin (mmol/mol)

  from diabetes diagnosis to study inclusion. (The study inclusion will be from 18 months after diagnosis to several years)

• Diagnostic of atypical diabetes using follow-up of laboratory results: Glycaemia

  Glycaemia (mg/dL)

  from diabetes diagnosis to study inclusion

• Diagnostic of atypical diabetes using follow-up of laboratory results: C-peptide

  C-peptide (pmol/mL)

  from diabetes diagnosis to study inclusion. (The study inclusion will be from 18 months after diagnosis to several years)

• Genetic diagnosis of diabetes: Anti-islets antibodies

  Presence of measurable Anti-islets antibodies

  from diabetes diagnosis to study inclusion. (The study inclusion will be from 18 months after diagnosis to several years)

• Genetic diagnosis of diabetes: HLA genotype

  Presence of at risk HLA genotype

  from diabetes diagnosis to study inclusion. (The study inclusion will be from 18 months after diagnosis to several years)

• Genetic diagnosis of atypical diabetes: MODY gene-sequencing test

  MODY gene-sequencing test (GCK, HNF1A, HNF4A, HNF1B, KCNJ11, ABCC8, and INS gene sequencing)

  at inclusion in the study

• Genetic diagnosis of atypical diabetes: More comprehensive genetic tests

  More comprehensive genetic tests will be conducted in patients without anomalies found after the MODY gene-sequencing test.

  After MODY gene-sequencing test, from 3 months to 1.5 year after study inclusion

Study Arms (2)

T1D Group

ACTIVE COMPARATOR

* Retrospective analysis of data from active and historical diabetic patients within diabetes care conventions of pediatric endocrinology services; screening of patients with atypical diabetes; use of tests used in clinical routine to allow referral to the genetic diagnosis of the condition. * Prospective analysis of the evolution of new diabetic patients followed in pediatric endocrinology services of diabetes care conventions; screening of patients with atypical diabetes; use of tests used in clinical routine to allow the genetic diagnosis of the condition. * Screening of patients with atypical diabetes: first evaluated according to the "MODY" probability calculator. In addition, other clinical criteria will be used to improve the sensitivity and specificity of pediatric monogenic diabetes screening.

Genetic: Mody test

MODY Group

EXPERIMENTAL

* Retrospective analysis of data from active and historical diabetic patients within diabetes care conventions of pediatric endocrinology services; screening of patients with atypical diabetes; use of tests used in clinical routine to allow referral to the genetic diagnosis of the condition. * Prospective analysis of the evolution of new diabetic patients followed in pediatric endocrinology services of diabetes care conventions; screening of patients with atypical diabetes; use of tests used in clinical routine to allow the genetic diagnosis of the condition. * Screening of patients with atypical diabetes: first evaluated according to the "MODY" probability calculator. In addition, other clinical criteria will be used to improve the sensitivity and specificity of pediatric monogenic diabetes screening.

Genetic: Mody test

Interventions

Mody test GENETIC

Subjects will be screened using a MODY gene-sequencing test, which includes GCK, HNF1A, HNF4A, HNF1B, KCNJ11, ABCC8, and INS gene sequencing. More comprehensive genetic tests will be conducted in patients without anomalies found after the MODY gene-sequencing test.

MODY Group; T1D Group

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age between 0 and 18 years at the age of diabetes diagnosis.
• Patients followed and/or diagnosed within diabetes care agreements of the pediatric endocrinology departments participating in the study.

You may not qualify if:

• none

Sponsors & Collaborators

• Université Catholique de Louvain: lead

Study Sites (1)

Cliniques universitaires Saint-Luc - UCLouvain

Brussels, 1200, Belgium

Location

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Philippe Lysy

  Cliniques universitaires Saint-Luc - UCLouvain

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 16, 2019
• Study Start: October 22, 2018
• Primary Completion: October 22, 2021
• Study Completion: June 22, 2022
• Last Updated: July 15, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)