Live Enterovirus Vaccine and Type 1 Diabetes

July 18, 2024 updated by: Hanna Viskari, Tampere University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

315

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 2 months (Child)

Accepts Healthy Volunteers

Yes

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Inactivated Polio Vaccine (IPV)
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.
Active Comparator: 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.
Biological: Oral Polio Vaccine (OPV)
Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Through study completion, an average of 11 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Enterovirus RNA Positive Stool Samples During the Follow-up of 24 Months
Time Frame: Up to 24 months of age
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tampere University

Investigators

  • Principal Investigator: Mikael Knip, Professor, Children's Hospital, University of Helsinki, and Helsinki University Central Hospital and Tampere University Hospital, Finland
  • Principal Investigator: Heikki Hyöty, Professor, University of Tampere, Finland
  • Principal Investigator: Hanna Viskari, MD,PhD, University of Tampere, Finland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 1999

Primary Completion (Actual)

November 1, 2016

Study Completion (Actual)

November 1, 2016

Study Registration Dates

First Submitted

November 2, 2016

First Submitted That Met QC Criteria

November 10, 2016

First Posted (Estimated)

November 11, 2016

Study Record Updates

Last Update Posted (Actual)

August 13, 2024

Last Update Submitted That Met QC Criteria

July 18, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 98203M Knip M

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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