Type 1 DiabetesGENEVIRNCT02804165
Gene-virus Interactions Implicated in Type 1 Diabetes
A study testing Enterovirus vaccination in people with Type 1 Diabetes, run by Hospices Civils de Lyon at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 60 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Enterovirus vaccination
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2017to Jul 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 15Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
- Conditions
- Type 1 Diabetes
- Being tested
- Enterovirus vaccination
- Keywords
- Type 1 diabetes, Enterovirus, Genetics, Gene-Virus interaction
- Medical subject headings
- Diabetes Mellitus, Type 1, Enterovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enterovirus vaccinationGenetic
Enterovirus vaccination in genetically predisposed subjects having a high risk to develop type 1 diabetes.
| Study group | Role | What they receive |
|---|---|---|
| Target high-risk subjects or subpopulations for T1D | Other | 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. Receives: Genetic: Enterovirus vaccination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of gene-enterovirus interaction effect on T1D onset
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.
Measured: 1 day
Secondary outcomes (1)
"Precipitating" effect of enterovirus infection on T1D.
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).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2016 (estimated)
- Study startJan 2017
- Primary completionJul 2022 (estimated)
- Study completionJul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marc Nicolino, MD, Principal investigator, HCL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02804165
- Sponsor's protocol ID
- 2013-836
- Acronym
- GENEVIR
- Status last verified
- May 2017
- First submitted
- 9 Jun 2016
- Last updated
- 11 May 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gene-virus Interactions Implicated in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT02804165
- Acronym / sponsor ID
- GENEVIR / 2013-836
- Conditions
- Type 1 Diabetes
- Keywords
- Type 1 diabetes, Enterovirus, Genetics, Gene-Virus interaction
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 17 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Target high-risk subjects or subpopulations for T1D | Other | Genetic: Enterovirus vaccinationConfirmation 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. |
Who may qualify
- Ages
- 1 year to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (7 listed)
- Adopted child
- For probands, being negative for T1D autoantibodies
- For probands, illness duration more than 6 months
- being negative for T1D autoantibodies
- T1D patient
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enterovirus vaccinationEnterovirus vaccination in genetically predisposed subjects having a high risk to develop type 1 diabetes. | Genetic | Target high-risk subjects or subpopulations for T1D |
Primary outcome
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.
1 secondary outcome
"Precipitating" effect of enterovirus infection on T1D.
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Nicolino, MD principal investigator
HCL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Enterovirus vaccination in people with Type 1 Diabetes, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of gene-enterovirus interaction effect on T1D onset (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2018.