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临床试验/NCT02961595
NCT02961595已完成1 期

Live Enterovirus Vaccine and Type 1 Diabetes

Tampere University0 个研究点目标入组 315 人开始时间: 1999年10月最近更新:
适应症

试验速览

阶段
1 期
状态
已完成
入组人数
315
主要终点
Number of Participants With the Appearance of Type 1 Diabetes Associated Auto-antibodies in Serum

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Parallel
主要目的
Prevention
盲法
None

入排标准

年龄范围
1 Day 至 2 Months(Child)
性别
All
接受健康志愿者

入选标准

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

排除标准

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

结局指标

主要结局

Number of Participants With the Appearance of Type 1 Diabetes Associated Auto-antibodies in Serum

时间窗: 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)

次要结局

  • Number of Enterovirus RNA Positive Stool Samples During the Follow-up of 24 Months(Up to 24 months of age)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Hanna Viskari

Researcher

Tampere University

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