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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.
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, xā DQB1*0201, *0301, *0602). Sixty-four children (34 males) were given doses of OPV (Polio SabinĀ®, 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 SabinĀ®) at the age of 2, 3, 6 and 12 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Polio Vaccine (OPV) | Biological | Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | Through study completion, an average of 11 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Up to 24 months of age |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mikael Knip, Professor | Children's Hospital, University of Helsinki, and Helsinki University Central Hospital and Tampere University Hospital, Finland | Principal Investigator |
| Heikki Hyƶty, Professor | University of Tampere, Finland | Principal Investigator |
| Hanna Viskari, MD,PhD | University of Tampere, Finland | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28866779 | Derived | 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. |
| Label | URL |
|---|---|
| The Diabetes Prediction and Prevention Project web pages | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Inactivated Polio Vaccine (IPV) | The control group received inactivated poliovirus vaccine (IPV) at the age of 6, 12 months and 2, 6 and 9-12 years according to the national immunization protocol in Finland at that time. |
| FG001 | Oral Polio Vaccine (OPV) | Intervention group were given doses of oral polio vaccine OPV (Polio SabinĀ®) at the age of 2, 3, 6 and 12 months. After the age of 12 months they were recommend to continue according to the national immunisation programme with IPV at the age of 2, 6 and 9-12 years. Oral Polio Vaccine (OPV): Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Inactivated Polio Vaccine (IPV) | The control group received inactivated poliovirus vaccine (IPV) at the age of 6, 12 months and 2, 6 and 9-12 years according to the national immunization protocol in Finland at that time. |
| BG001 | Oral Polio Vaccine (OPV) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | Posted | Count of Participants | Participants | Through study completion, an average of 11 years |
|
Adverse events were assessed at the study clinic visits during follow-up of two years (3, 6, 9, 12, 18 and 24 months of age) and thereafter at follow-up visits trough study completion if reported
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Inactivated Polio Vaccine (IPV) | The control group received inactivated poliovirus vaccine (IPV) at the age of 6 and 12 months and 2, 6, and 9-12 years according to the national immunization protocol in Finland at that time. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hanna Viskari | University of Tampere | hanna.viskari@uta.fi |
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| ID | Term |
|---|---|
| D004769 | Enterovirus Infections |
| D003922 | Diabetes Mellitus, Type 1 |
| D011236 | Prediabetic State |
| ID | Term |
|---|---|
| D010850 | Picornaviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D011055 | Poliovirus Vaccine, Oral |
| ID | Term |
|---|---|
| D023321 | Poliovirus Vaccines |
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
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Intervention group were given doses of oral polio vaccine OPV (Polio SabinĀ®) at the age of 2, 3, 6 and 12 months. After the age of 12 months they were recommend to continue according to the national immunisation programme with IPV at the age of 2, 6 and 9-12 years. Oral Polio Vaccine (OPV): Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV). |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | 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 | Overall 1488 stools samples were collected and analysed from 3 to 24 months in both IPV and OPV groups | Posted | Count of Units | stool samples | Up to 24 months of age | stool samples | stool samples |
|
|
|
| 0 |
| 251 |
| 0 |
| 251 |
| 0 |
| 251 |
| EG001 | Oral Polio Vaccine (OPV) | Intervention group were given doses of oral polio vaccine OPV (Polio SabinĀ®) at the age of 2, 3, 6 and 12 months. After the age of 12 months they were recommended to continue according to the national immunisation programme with IPV at the age of 2, 6 and 9-12 years. Oral Polio Vaccine (OPV): Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV). | 0 | 64 | 0 | 64 | 0 | 64 |
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| D003920 |
| Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D045424 |
| Complex Mixtures |