Identification and Characterization of Monogenic Diabetes

Diabetes Clinical Trial

— DIAGENE  

Official title:

Identification and Genetic, Clinical and Metabolic Characterization of Monogenic Forms of Insulin-dependent Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01481623
• Other study ID #: P081230
• Status: Recruiting
• Phase: N/A
• First received: October 27, 2011
• Last updated: June 1, 2015
• Start date: September 2012
• Est. completion date: September 2015

Study information

• Verified date: May 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Pierre-Jean Guillausseau, MD
• Phone: +33 (0)1 49 95 63 80
• Email: pierre-jean.guillausseau[@]lrb.aphp.fr
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Type 1 Diabetes is a multifactorial disease, with a strong genetic contribution of HLA genes, and minor contributions of many additional genes. The investigators hypothesis is that in addition to multifactorial inheritance, there are subtypes of diabetes that are caused by defects in single genes (monogenic diabetes). The aim of this project is to identify these genes, based on detailed clinical and characterization of patients, and to describe the corresponding genetic diabetes entities with respect to the genetic and molecular defect, clinical features and biochemistry. Based on the investigators study design, most of these diabetes entities will be caused by mutations affecting the two copies of the corresponding gene. In addition, the investigators will study the relatives of the patients, and explore if carriers of these genetic defects (i.e. only one copy of the gene being defective) may have a predisposition to common forms of diabetes, mainly type 2 diabetes.

Description:

In the first phase of the study the investigators will recruit patients and families, with a strong bias for "extreme" forms of diabetes (very early onset and/or syndromic diabetes) and familial context suggestive of monogenic inheritance (e.g. consanguinity, multiplicity of diabetic siblings) and perform genetic studies on these to identify the genes. After obtaining informed consent, the investigators will collect clinical information on diabetes and other associated diseases and features, family information on diabetes, and collect blood samples for DNA, RNA, serum and cell lines. The investigators will then perform genetic studies to identify the genes responsible for these monogenic forms of diabetes.

After identification of genes, the second phase of the study will be to test the consequence of carrier status for the identified mutations on metabolic traits related to glucose metabolism. For this, after obtaining informed consent, the investigators will extend the recruitment of the initial families (after gene identification) to recruit relatives who may be carriers of these mutations. The investigators will determine the carrier status of these subjects and perform a detailed clinical description as well as metabolic studies to evaluate their glucose metabolism.

This study will lead to the identification of new monogenic diabetes entities, and their corresponding genes, and may also result in the identification of new genes predisposing to common forms of diabetes. This project has implication for diagnosis of these monogenic forms of diabetes, and may result in some cases in improved care for the patients, including prevention and treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• First phase: to have an "extreme" form of diabetes, based on clinical, phenotypic and familial criteria. Parents and siblings of the proband will be sampled.

• Second phase: (after gene identification): to be a relative of the proband, potential carrier of the mutation

Exclusion Criteria:

• Non consent to participate to the study

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Diabetes

Intervention

Other:
• Constitution of a biological bank
Blood samples for the constitution of a biobank (DNA, RNA, serum)
• Metabolic studies
oral glucose tolerance test (OGTT) intravenous glucose tolerance test (IVGTT) hyperglycemic clamp staged glucose perfusion arginine test measure of body composition (BIPHOTONIC absorptiometry, DEXA)

Locations

Country	Name	City	State
France	Lariboisiere hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification and genetic, clinical and metabolic characterization of monogenic diabetes forms	to identify genes responsible for monogenic insulin-dependant diabetes, and to define and characterize the corresponding genetic diabetes entities with respect to the genetic and molecular defect, clinical and phenotypic features and biochemistry	36 months	No
Secondary	Diagnosis of monogenic diabetes	to diagnose these monogenic diabetes entities and to evaluate the proportion of insulin-dependant diabetes which are explained by monogenic determinism, depending on several parameters, such as familial structure and clinical characteristics.	36 months	No
Secondary	Clinical and biological characterization of total or partial deficiency of the genes responsible for monogenic diabetes	To characterize precisely the clinical and biological consequences of total or partial deficiency of the genes responsible for monogenic diabetes, and explore their possible role in glucidic metabolism. This way suggest them as candidate genes for common forms of diabetes.	36 months	No