Live Enterovirus Vaccine and Type 1 Diabetes

Type 1 Diabetes Clinical Trial

Official title:

Live Enterovirus Vaccine and Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02961595
• Other study ID #: 98203M Knip M
• Status: Completed
• Phase: Phase 1
• First received: November 2, 2016
• Last updated: November 10, 2016
• Start date: October 1999
• Est. completion date: November 2016

Study information

• Verified date: November 2016
• Source: University of Tampere
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Finnish Medicines Agency
• Study type: Interventional

Clinical 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 to other enteroviruses and the possible initiation of autoantibodies e.g. islet autoimmunity in young genetically predisposed children.

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 poliovaccination 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 315
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 2 Months

Eligibility

Inclusion Criteria:

• The infants parents give signed consent to participate and their HLA genotype is eligible

Exclusion Criteria:

• The newborn has a recognizable severe illness such as those due to chromosomal abnormality, congenital malformation

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Enterovirus Infection
• Enterovirus Infections
• Prediabetic State
• Type 1 Diabetes

Intervention

Biological:
• Oral Polio Vaccine (OPV)
Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Tampere

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Appearance of type 1 diabetes associated auto-antibodies in serum		Through study completion, an average of 11 years	No
Secondary	Presence of enterovirus RNA in stools		Up to 24 months of age	No

External Links

•   The Diabetes Prediction and Prevention Project web pages