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Trial record 24 of 2791 for:    Type 1 Diabetes

Gene-virus Interactions Implicated in Type 1 Diabetes (GENEVIR)

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ClinicalTrials.gov Identifier: NCT02804165
Recruitment Status : Not yet recruiting
First Posted : June 17, 2016
Last Update Posted : December 8, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

Type 1 diabetes (T1D) is the most common endocrine disorder in children. In France, T1D prevalence is estimated to 12.2 per 100 000. Worldwide T1D incidence increased rapidly in the last decades, around 3% per year. T1D is caused by autoimmune destruction of pancreatic beta cells, leading to hyperglycaemia. T1D was recently associated an important loss in life expectancy compared with the general population. To date, the precise aetiology of T1D onset and the mechanisms involved in T1D remain unknown and no preventive treatment of T1D exists.

It is now well admitted that T1D results from a combined effect of genes, environmental factors and gene-environment interactions. Several genetic factors have been reported as associated to T1D, the most important being the human leukocyte antigen class II genes. Whole genome association studies suggested more than 50 T1D other susceptibility locus, but conferring individually a modest risk to develop T1D. Longitudinal studies demonstrated that only a low fraction of genetically predisposed subjects develop T1D and all these genetic factors cannot explain the increase in prevalence of T1D in the latter half of the 20th century, suggesting the implication of environmental factors.

Literature has accumulated a lot of evidence for the role of enterovirus in T1D. Several retrospective, prospective, post-mortem human studies, as well as animal studies, strongly suggest contribution of human enteroviruses to the pathogenesis of T1D. Enterovirus probably play a dual role in T1D, some enterovirus being associated with an increased risk of T1D and others with a protective effect. Interestingly, several T1D susceptibility loci are implicated in antiviral response. Epidemiologic and genetic approaches have led to new insights into T1D causation, but a collective explanation is still lacking.

The project aims at (1) demonstrating the gene-enterovirus interaction effect on T1D onset and (2) characterizing the "precipitating" effect of enterovirus on T1D by a follow-up study of T1D high-risk subjects (first degree unaffected relatives with positive autoantibodies to islet antigens).

A structural originality of this project is to perform a family-based study of gene-enterovirus interaction in T1D using innovative and robust methods. This project will be conducted in close collaboration between our INSERM unit, the Inter-regional network of paediatric diabetology, labelled biobanks (CBC Biotec of Hospices Civils de Lyon and CRB-LRB of Lariboisière' hospital at Paris), the Centre National de Référence des Enterovirus at Lyon and the Centre National de Génotypage at Evry.

The investigators will first conduct a 3-years pilot study (2016-2019), based on a sample of 250 nuclear families ascertained through a paediatric T1D proband in four centres. Families will be ascertained during the hospitalization of the proband at the time of T1D diagnosis. The study will be then extended to whole Inter-regional network of paediatric diabetology.

This research is a unique opportunity to explore further the implication of enterovirus and their interactions with genetic factors involved in T1D susceptibility and aims to target high-risk T1D subjects. This innovative project opens the door of the development of preventive therapy for T1D.

Condition or disease Intervention/treatment
Type 1 Diabetes Genetic: Enterovirus vaccination

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Gene-virus Interactions Implicated in Type 1 Diabetes
Anticipated Study Start Date : December 2017
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Target high-risk subjects or subpopulations for T1D
Confirmation of the role of enteroviral infection in T1D and characterization of gene-enterovirus interactions should open up new avenues for understanding the pathogenesis of T1D and give clues on possible new therapeutic perspectives. Clinical applications might be further developed in order to extend the lag period might between positive autoantibodies detection and T1D age at onset in genetically predisposed subjects. This innovative project opens the door of the development of preventive therapy for T1D, as enterovirus vaccination.
Genetic: Enterovirus vaccination
Enterovirus vaccination in genetically predisposed subjects having a high risk to develop type 1 diabetes.

Outcome Measures

Primary Outcome Measures :
  1. Identification of gene-enterovirus interaction effect on T1D onset [ Time Frame: 1 day ]
    The investigators choose to use a family-based approach in order to capture the underlying complexities of gene-environment interactions by identifying families with combinations of risk factors (genetic and enterovirus) that lead to disease expression. The gene-environment studies will be conducted for different candidate genes significantly associated with T1D. Families will be ascertained during the hospitalization of probands at the moment of T1D diagnosis. DNA, plasma, serum and stool samples will be collected for viral detection and genotyping. Gene-enterovirus effect will be estimated by using the "sibling-augmented case-only" approach based on logistic models.

Secondary Outcome Measures :
  1. "Precipitating" effect of enterovirus infection on T1D. [ Time Frame: 2 years ]
    Enterovirus infection "precipitating" effect will be tested by a survival analysis using the Cox semiparametric proportional hazards model, expressing the instantaneous hazard rate of T1D according to the status towards the enterovirus and covariates (age and gender).

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

For Families :

For probands

  • new-onset T1D (less than six months)
  • aged between 2 and 15 years
  • positive for T1D autoantibodies
  • having at least one sib who accepts to participate to the study
  • sign an informed consent form.

For relatives

  • aged between 1 and 60 years
  • having at least one sib (or child for parents) included in the study
  • sign an informed consent form.

For unaffected T1D first degree relatives carrying antibodies to islet antigens:

  • aged between 1 and 60 years
  • being carrier of antibodies to islet antigens.
  • having at least one sib (or child for parents) included in the study

Exclusion Criteria:

For Families :

  • Adopted child
  • For probands, being negative for T1D autoantibodies
  • For probands, illness duration more than 6 months

For unaffected T1D first degree relatives carrying antibodies to islet antigens:

  • being negative for T1D autoantibodies
  • T1D patient
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02804165

Contact: Marc Nicolino, MD (0)472129524 ext +33 marc.nicolino@chu-lyon.fr

Hospices Civils de Lyon
Lyon, France, 69000
Sponsors and Collaborators
Hospices Civils de Lyon
Principal Investigator: Marc Nicolino, MD HCL
More Information

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT02804165     History of Changes
Other Study ID Numbers: 2013-836
First Posted: June 17, 2016    Key Record Dates
Last Update Posted: December 8, 2017
Last Verified: May 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hospices Civils de Lyon:
Type 1 diabetes
Gene-Virus interaction

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Immunologic Factors
Physiological Effects of Drugs