Diabetes Virus Detection
and Intervention Trial (DiViDInt)

EudraCT Number: 2015-003350-41

Accumulating evidence suggest that viruses may be an important factor in the pathogenesis of type 1 diabetes. We recently demonstrated a lowgrade, persistent enterovirus infection in the pancreatic islets of Langerhans of live patients at the diagnosis of T1D, and that about one third of the islets still produced insulin. We now want to test whether antiviral treatment may stop the disease process and maintain residual insulin production. Patients 5-16 years of age participate in a randomized, double blinded, placebo controlled trial of antiviral treatment with the combination of oral Pleconaril and Ribavirin. Study sites: Oslo and Copenhagen. All patients receive modern, intensified insulin treatment with insulin pumps or pens. Study drug treatment or placebo started within three weeks after diagnosis of T1D and last for 6 months. Follow-up at 3, 6, 12, 24, and 36 months. In October 2020 we included the last of the 96 patients according to protocol. 

Endpoints: Change in mean residual insulin secretion measured by stimulated C-peptide (MMTT) and number of patients with clinical significant C-peptide.

Fasting and meal stimulated C-peptide from blood sampled monthly at home. Insulin dosage. HbA1c. Hypoglycemic events. Proinsulin/c-peptide ratio in serum as a measure of beta cell stress. Change in presence of Enterovirus in nose, blood and stool.

If antiviral treatment is effective, it will add proof to the concept that type 1 diabetes in its origin may be a viral disease. This would be an important milestone in medical research and be a breakthrough to the understanding of the etiopathogenesis of autoimmune diseases. It may promote the development of vaccines to prevent the disease.

READ MORE 

News from 2024:

Primary endpoint was met after one year. The primary endpoint was residual insulin production (C-peptide AUC) at 12 months which was found to be significantly higher in the group that received antiviral medication compared to the group that received the placebo. The results were published in Nature Medicine. The publication has been selected as one of the best medical scientific articles in Norway for 2023 and was presented for the Health Minister in May 2024. At the final analysis of the trial this primary endpoint effect was even stronger, but unfortunately this positive effect faded after three years follow-up.

Publications 2024

  1. Mynarek IM, Krogvold L, Mørk FB, Lawaetz TWH, Roald T, Fagerland MW, Lindblom N, Westman J, Barker P, Hyöty H, Ludvigsson J, Hanssen KF, Johannesen J, Dahl-Jørgensen K. Three-Year Follow-up After Antiviral Treatment in New-Onset Type 1 Diabetes: Results From the Diabetes Virus Detection and Intervention Trial. Diabetes Care. 2025 Mar 1;48(3):481-488. doi: 10.2337/dc24-2121. PMID: 39804800 Clinical Trial.

  2. Ravlo E, Ianevski A, Schjølberg JO, Solvang V, Dumaru R, Lysvand H, Hankinson J, Vähä-Koskela M, Vainionpää S, Varhe A, Seppänen H, Smura T, Wang X, Wang Y, Li P, Pan Q, Dahl-Jorgensen K, Krogvold L, Kamyshnyi O, Nilsen HS, Haugen IJ, Høyer E, Afset JE, Oksenych V, Galabov AS, Stoyanova A, Lam V, van Loon B, Lulla V, Bjørås M, Kainov DE. Synergistic combination of orally available safe-in-man pleconaril, AG7404, and mindeudesivir inhibits enterovirus infections in human cell and organoid cultures. Cell Mol Life Sci. 2025 Jan 23;82(1):57. doi: 10.1007/s00018-025-05581-4. PMID: 39843710 Free PMC article.

Primary Investigators:

Co-investigators/participants:

  • Ida Mynarek, Physician, PhD student. Pediatric Dept. Oslo University Hospital

  • Trine Roald, Study Nurse, Pediatric Dept. Oslo University Hospital 

  • Erica Ponzi, Statistician, PhD, Oslo University Hospital 

  • Kristian F. Hanssen, Senior Professor, University of Oslo

External collaborators: 

  • Jesper Johannesen, Professor, Pediatric Dept. Herlev Hospital, Steno Center, Copenhagen 

  • Heikki Hyöty, Professor, Dept of Virology, University of Tampere, Finland

  • Johnny Ludvigsson, Professor, Dept. of Pediatrics, University of Linköping, Sweden

  • Mikael Knip, Professor, Dept. of Pediatrics, University of Helsinki, Finland  

  • Peter Barker, Professor, University of Cambridge, UK

  • Adrian Mander, Statistician, Professor, University of Cardiff, UK

  • Freja Barrett Mørk, Physician, PhD student, Pediatric Dept. Herlev Hospital, Steno Center, Copenhagen 

  • Trine Witzner Hessel, Physician, PhD student, Pediatric Dept. Herlev Hospital, Steno Center, Copenhagen