Enterovirus InfectionPhase 1NCT02961595
Live Enterovirus Vaccine and Type 1 Diabetes
A Phase 1 study testing Oral Polio Vaccine (OPV) in people with Enterovirus Infection and Type 1 Diabetes, run by Tampere University.
Trial summary
Enterovirus infections may either increase or decrease the risk of type 1 diabetes depending on the age of infection and the type of enterovirus in question. This study evaluated whether early serial exposures to three replication-competent enterovirus strains (live poliovirus vaccine, OPV) can influence the immunity… Read more about this study
- Who is it for?
- Ages 1 day to 2 monthsHealthy volunteers can take part
- Conditions the study is for
- Enterovirus Infection, Type 1 Diabetes, Prediabetic State
- What is being tested?
- Oral Polio Vaccine (OPV)
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 315 participants
- Where
- No sites listed yet
- Study dates
- Oct 1999to Nov 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 day to 2 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- The infants parents give signed consent to participate and their HLA genotype is eligible
Who cannot join
- The newborn has a recognizable severe illness such as those due to chromosomal abnormality, congenital malformation
About this study
Enterovirus infections may either increase or decrease the risk of type 1 diabetes depending on the age of infection and the type of enterovirus in question. This study evaluated whether early serial exposures to three replication-competent enterovirus strains (live poliovirus vaccine, OPV) can influence the immunity to other enteroviruses and the possible initiation of autoantibodies e.g. islet autoimmunity in young genetically predisposed children.
Read the detailed description
Enteroviruses have been associated with type 1 diabetes in several studies. Enterovirus infections may either increase or decrease the risk of type 1 diabetes depending on the age of infection and the type of enterovirus in question. There is remarkable homology between the structure of poliovirus and other enteroviruses. It has been shown in previous studies that the T-lymphocytes recognize these structures and cross-react with different enterovirus serotypes. Our hypothesis is that polio vaccination induces a cross-reacting T-cell response which strengthens enterovirus immunity and thus accelerate the elimination of the enterovirus infections. We evaluated whether early serial live enterovirus vaccine (oral polio vaccine, OPV) can influence the enterovirus immunity and initiation of islet autoimmunity in young genetically predisposed children.
This study was carried out in the birth cohort of the ongoing Diabetes Prediction and Prevention (DIPP) study in Finland. All the children carried HLA-DQ genes conferring moderately increased risk for type 1 diabetes (HLA DQB1*0302/x, x≠ DQB1*0201, *0301, *0602). Sixty-four children (34 males) were given doses of OPV (Polio Sabin®, SB Biologicals, Rixensart, Belgium) at the age of 2, 3, 6 and 12 months during the years 1999-2000 (two drops per os in each dose). This vaccine includes attenuated replication competent strains of the three poliovirus types (polioviruses 1, 2, 3) leading to infection in vaccinated children. The control group comprising 251 children received inactivated poliovirus vaccine (IPV) at the age of 6 and 12 months according to the national immunization protocol in Finland at that time. After the age of 12 months both groups were recommended to continue the national immunization program with IPV vaccine.
All children were followed regularly from birth with blood samples taken at 3-12 months interval for detection of type 1 diabetes-associated autoantibodies in serum including insulin autoantibodies (IAA), islet cell cytoplasmic antibody (ICA), insulinoma-associated protein 2 antibodies (IA-2A) and GAD antibodies (GADA) (5-7). Stool samples were collected monthly at the age of 2-24 months and systematically screened for the presence of enterovirus and using RT-PCR.
- Conditions
- Enterovirus Infection, Type 1 Diabetes, Prediabetic State
- Being tested
- Oral Polio Vaccine (OPV)
- Keywords
- Oral polio vaccine, Inactivated polio vaccine, Enterovirus, Type 1 diabetes, Autoantibody
- Medical subject headings
- Enterovirus Infections, Diabetes Mellitus, Type 1, Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Polio Vaccine (OPV)Biological
Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV).
| Study group | Role | What they receive |
|---|---|---|
| Inactivated Polio Vaccine (IPV) | No intervention | The control group received inactivated poliovirus vaccine (IPV) at the age of 6 and 12 months according to the national immunization protocol in Finland at that time. |
| Oral Polio Vaccine (OPV) | Active comparator | Intervention group were given doses of oral polio vaccine OPV (Polio Sabin®) at the age of 2, 3, 6 and 12 months. Receives: Biological: Oral Polio Vaccine (OPV) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With the Appearance of Type 1 Diabetes Associated Auto-antibodies in Serum
Appearance of multiple type 1 diabetes associated auto-antibodies (2-4 of the measured four auto-antibodies ICA, IAA, GADA, IA-2A)
Measured: Through study completion, an average of 11 years
Secondary outcomes (1)
Number of Enterovirus RNA Positive Stool Samples During the Follow-up of 24 Months
Percentage of enterovirus RNA positive stool samples during the follow-up of 24 months in IPV and OPV vaccinated children
Measured: Up to 24 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2016 (estimated)
- Study startOct 1999
- Primary completionNov 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Enterovirus InfectionStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 315 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tampere University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hanna Viskari, Tampere University
- Investigators
- Mikael Knip, Professor, Principal investigator, Children's Hospital, University of Helsinki, and Helsinki University Central Hospital and Tampere University Hospital, FinlandHeikki Hyöty, Professor, Principal investigator, University of Tampere, FinlandHanna Viskari, MD,PhD, Principal investigator, University of Tampere, Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02961595
- Sponsor's protocol ID
- 98203M Knip M
- Status last verified
- Jul 2024
- First submitted
- 2 Nov 2016
- Last updated
- 13 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Viskari H, Oikarinen S, Hoppu S, Vuorinen T, Huhtala H, Toppari J, Veijola R, Ilonen J, Knip M, Hyoty H. Live attenuated enterovirus vaccine (OPV) is not associated with islet autoimmunity in children with genetic susceptibility to type 1 diabetes: prospective cohort study. Diabetologia. 2018 Jan;61(1):203-209. doi: 10.1007/s00125-017-4410-4. Epub 2017 Sep 2.
PubMed 28866779
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Live Enterovirus Vaccine and Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT02961595
- Acronym / sponsor ID
- 98203M Knip M
- Conditions
- Enterovirus Infection, Type 1 Diabetes, Prediabetic State
- Keywords
- Oral polio vaccine, Inactivated polio vaccine, Enterovirus, Type 1 diabetes, Autoantibody
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 315 participants (actual)
- Lead sponsor
- Tampere UniversityUniversity, hospital or other
- Study start
- Oct 1999
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 11 Nov 2016 (estimated)
- Results
- Posted 18 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Enterovirus infections may either increase or decrease the risk of type 1 diabetes depending on the age of infection and the type of enterovirus in question. This study evaluated whether early serial exposures to three replication-competent enterovirus strains (live poliovirus vaccine, OPV) can influence the immunity to other enteroviruses and the possible initiation of autoantibodies e.g. islet autoimmunity in young genetically predisposed children.
Detailed description
Enteroviruses have been associated with type 1 diabetes in several studies. Enterovirus infections may either increase or decrease the risk of type 1 diabetes depending on the age of infection and the type of enterovirus in question. There is remarkable homology between the structure of poliovirus and other enteroviruses. It has been shown in previous studies that the T-lymphocytes recognize these structures and cross-react with different enterovirus serotypes. Our hypothesis is that polio vaccination induces a cross-reacting T-cell response which strengthens enterovirus immunity and thus accelerate the elimination of the enterovirus infections. We evaluated whether early serial live enterovirus vaccine (oral polio vaccine, OPV) can influence the enterovirus immunity and initiation of islet autoimmunity in young genetically predisposed children.
This study was carried out in the birth cohort of the ongoing Diabetes Prediction and Prevention (DIPP) study in Finland. All the children carried HLA-DQ genes conferring moderately increased risk for type 1 diabetes (HLA DQB1*0302/x, x≠ DQB1*0201, *0301, *0602). Sixty-four children (34 males) were given doses of OPV (Polio Sabin®, SB Biologicals, Rixensart, Belgium) at the age of 2, 3, 6 and 12 months during the years 1999-2000 (two drops per os in each dose). This vaccine includes attenuated replication competent strains of the three poliovirus types (polioviruses 1, 2, 3) leading to infection in vaccinated children. The control group comprising 251 children received inactivated poliovirus vaccine (IPV) at the age of 6 and 12 months according to the national immunization protocol in Finland at that time. After the age of 12 months both groups were recommended to continue the national immunization program with IPV vaccine.
All children were followed regularly from birth with blood samples taken at 3-12 months interval for detection of type 1 diabetes-associated autoantibodies in serum including insulin autoantibodies (IAA), islet cell cytoplasmic antibody (ICA), insulinoma-associated protein 2 antibodies (IA-2A) and GAD antibodies (GADA) (5-7). Stool samples were collected monthly at the age of 2-24 months and systematically screened for the presence of enterovirus and using RT-PCR.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inactivated Polio Vaccine (IPV) | No intervention | –The control group received inactivated poliovirus vaccine (IPV) at the age of 6 and 12 months according to the national immunization protocol in Finland at that time. |
| Oral Polio Vaccine (OPV) | Active comparator | Biological: Oral Polio Vaccine (OPV)Intervention group were given doses of oral polio vaccine OPV (Polio Sabin®) at the age of 2, 3, 6 and 12 months. |
Who may qualify
- Ages
- 1 day to 2 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- The infants parents give signed consent to participate and their HLA genotype is eligible
Key exclusion criteria (1 listed)
- The newborn has a recognizable severe illness such as those due to chromosomal abnormality, congenital malformation
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 |
|---|---|---|
| Oral Polio Vaccine (OPV)Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV). | Biological | Oral Polio Vaccine (OPV) |
Primary outcome
Number of Participants With the Appearance of Type 1 Diabetes Associated Auto-antibodies in Serum
Time frame: Through study completion, an average of 11 years
Appearance of multiple type 1 diabetes associated auto-antibodies (2-4 of the measured four auto-antibodies ICA, IAA, GADA, IA-2A)
1 secondary outcome
Number of Enterovirus RNA Positive Stool Samples During the Follow-up of 24 Months
Time frame: Up to 24 months of age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28866779Viskari H, Oikarinen S, Hoppu S, Vuorinen T, Huhtala H, Toppari J, Veijola R, Ilonen J, Knip M, Hyoty H. Live attenuated enterovirus vaccine (OPV) is not associated with islet autoimmunity in children with genetic susceptibility to type 1 diabetes: prospective cohort study. Diabetologia. 2018 Jan;61(1):203-209. doi: 10.1007/s00125-017-4410-4. Epub 2017 Sep 2.
- The Diabetes Prediction and Prevention Project web pagesLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Mikael Knip, Professor principal investigator
Children's Hospital, University of Helsinki, and Helsinki University Central Hospital and Tampere University Hospital, Finland
Heikki Hyöty, Professor principal investigator
University of Tampere, Finland
Hanna Viskari, MD,PhD principal investigator
University of Tampere, Finland
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Oral Polio Vaccine (OPV) in people with Enterovirus Infection and Type 1 Diabetes, run by Tampere University.
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 1 inclusion and 1 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: finished, as of the sponsor's last update on 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With the Appearance of Type 1 Diabetes Associated Auto-antibodies in Serum (time frame: Through study completion, an average of 11 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02961595, which also lists 1 linked publication.
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 13 Aug 2024.