The project will utilise samples and data from the following existing cohorts and trials; selected sub-cohorts will be analysed in ENT1DEP.
The Finnish Diabetes Prediction and Prevention (DIPP) birth-cohort study
DIPP recruits children with increased T1D HLA class II genetic risk and follows them every 3-12 months from birth until 15 years of age or clinical T1D diagnosis (Partner 8-TAUH). Blood samples are collected for autoantibody (AAb) analyses (IAA, GADA, IA-2A, ZnT8A) and serum, plasma, buffy-coat and PBMC biobanking, with monthly stool samples for virus analyses. To date, >20,000 children have been followed up, >1,100 seroconverted for multiple AAbs (stage 1-2 T1D) and >500 developed clinical (stage 3) T1D. DIPP study is still recruiting.
More information: https://dipp.fi/?page_id=2684&lang=en
Australian Environmental Determinants of Islet Autoimmunity (ENDIA) birth-cohort study and biobank
ENDIA, provides similar samples and data as DIPP from a different population for validation. Currently ENDIA cohort includes 1473 children who have been followed from birth (58 have developed AAbs). ENDIA study is still recruiting.
More information: https://www.endia.org.au/
The Environmental Determinants of Diabetes in the Young (TEDDY) birth-cohort study
TEDDY is a birth cohort study recruiting children in the U.S., Germany, Sweden and Finland to a follow-up from the age of 3 months to 15 years11. The cohort includes 8.667 children, >500 have developed multiple AAbs and >430 T1D. Longitudinal data on stool virome (Illumina mass sequencing), whole blood transcriptomics (Illumina bead array and RNA-Seq), proteomics, whole genome sequencing, plasma cytokines and genetics is available. Partners 1-TAU and 8-TAUH are active participants of TEDDY study and collaborate with TEDDY Data Coordination Center in the analysis of this data in ENT1DEP (manuscript proposals covering these analyses has been accepted by TEDDY).
More information: https://teddy.epi.usf.edu/
Diabetes Virus Detection Study (DiViD) study
DiViD has collected pancreas biopsies from 6 living newly diagnosed T1D patients. It is the first study to provide pancreatic tissue biopsies of unique quality at the time of diagnosis with several aliquots of frozen and formalin embedded samples to study the pathogenesis of type 1 diabetes. Duodenal biopsies were collected by gastroscopy. Serum, PBMCs and serum/plasma were also collected. All patients had HLA-risk for T1D and at least one positive autoantibody. The study started in 2009 and ended in 2012.
More information: https://www.oslodiabetes.no/diabetes-virus-detection-study-divid
Network for Pancreatic Organ Donors with Diabetes (nPOD) consortium
nPOD collects well-preserved pancreas samples from cadaver organ donors with T1D and control donors (198 T1D, 55 IA+ and 268 control donors). These tissues are distributed widely to different research groups upon accepted request. Tampere University has been involved in the establishment of nPOD being an active participant of nPOD from its beginning and have access to these samples. nPOD continues collecting samples.
More information: https://npod.org/about/mission/
PROVENT trial
A phase 1, first-in-human, randomized, double-blind, placebo-controlled, study in Finland was carried out to evaluate the safety and immunogenicity of PRV-101, an inactivated multivalent CVB vaccine, in 32 healthy volunteers who were enrolled to receive vaccine (N=24) or placebo (N=8) in 3 intramuscular injections at 4-week intervals and to be followed for 24 weeks after the final dose. Primary outcome measure was adverse events (safety and tolerability) and secondary outcome neutralizing antibodies to CVBs (immunogenicity, efficacy). Trial started in 12/2020 and ended in 12/2021. ClinicalTrials.gov Identifier: NCT04690426.
DIVIDInt trial
A double-blind, placebo controlled, prospective, randomized trial examining the effect of antiviral treatment given for 6 months on residual insulin secretion in 96 newly diagnosed T1D patients (age 6-15 years) carried out by Oslo University Hospital in Norway and Denmark. Participants were randomized to receive either a combination of ribavirin and pleconaril which are known to be effective against EVs or placebo (1:1). Primary end point was a change in mean residual insulin secretion in Mixed Meal Tolerance Test stimulated C-peptide from visit 1 to 12 months after initiation of study treatment. The results showed better preservation of beta-cell function in the treatment arm (submitted for publication). The trial started in 8/2018 and ended in 10/2020. ClinicalTrials.gov Identifier: NCT04838145.