Intranasal Insulin for Prevention of Type 1 Diabetes
Summary
Children born in Turku, Oulu and Tampere university cities in Finland are screened at birth for HLA alleles that carry increased risk to or protection from development of type 1 diabetes. Children carrying increased risk are followed at 3-12-month intervals for development of diabetes-associated autoantibodies. Children having at least two types of autoantibodies (of the four measured) in at least two consecutively drawn samples are randomized to receive daily intranasal insulin or placebo in a double-blinded 1:1 trial. Hypothesis is that intranasal insulin delays or prevents development of clinical type 1 diabetes. The primary outcome measure is development of clinical diabetes.
Timeline
- Start
- 1997-08
- Primary completion
- —
- Completion
- 2005-08
Outcome
Missed primary endpoint
paper In all randomised children, diabetes was diagnosed in 56 in the insulin group, and 53 in the placebo group (HR 0.98; 0.67-1.43, p=0.91). PMID 18814906 ↗
paper administration of nasal insulin, started soon after detection of autoantibodies, could not be shown to prevent or delay type 1 diabetes. PMID 18814906 ↗
Publications
- Background Kupila A, Sipila J, Keskinen P, Simell T, Knip M, Pulkki K, Simell O. Intranasally administered insulin intended for prevention of type 1 diabetes--a safety study in healthy adults. Diabetes Metab Res Rev. 2003 Sep-Oct;19(5):415-20. doi: 10.1002/dmrr.397.
- Background Keskinen P, Korhonen S, Kupila A, Veijola R, Erkkila S, Savolainen H, Arvilommi P, Simell T, Ilonen J, Knip M, Simell O. First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes. Diabetologia. 2002 Dec;45(12):1639-48. doi: 10.1007/s00125-002-0981-8. Epub 2002 Oct 30.
- Background Kupila A, Keskinen P, Simell T, Erkkila S, Arvilommi P, Korhonen S, Kimpimaki T, Sjoroos M, Ronkainen M, Ilonen J, Knip M, Simell O. Genetic risk determines the emergence of diabetes-associated autoantibodies in young children. Diabetes. 2002 Mar;51(3):646-51. doi: 10.2337/diabetes.51.3.646.
- Background Hermann R, Mantere J, Lipponen K, Veijola R, Soltesz G, Otonkoski T, Simell O, Knip M, Ilonen J. Lack of association of PAX4 gene with type 1 diabetes in the Finnish and Hungarian populations. Diabetes. 2005 Sep;54(9):2816-9. doi: 10.2337/diabetes.54.9.2816.
- Background Kukko M, Toivonen A, Kupila A, Korhonen S, Keskinen P, Veijola R, Virtanen SM, Ilonen J, Simell O, Knip M. Familial clustering of beta-cell autoimmunity in initially non-diabetic children. Diabetes Metab Res Rev. 2006 Jan-Feb;22(1):53-8. doi: 10.1002/dmrr.584.
- Virtanen SM, Nevalainen J, Kronberg-Kippila C, Ahonen S, Tapanainen H, Uusitalo L, Takkinen HM, Niinisto S, Ovaskainen ML, Kenward MG, Veijola R, Ilonen J, Simell O, Knip M. Food consumption and advanced beta cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes: a nested case-control design. Am J Clin Nutr. 2012 Feb;95(2):471-8. doi: 10.3945/ajcn.111.018879. Epub 2012 Jan 11.
- Goldstein E, Hermann R, Renfors TJ, Nanto-Salonen KM, Korhonen T, Karkkainen M, Veijola RK, Knip M, Simell TT, Simell OG. From genetic risk awareness to overt type 1 diabetes: parental stress in a placebo-controlled prevention trial. Diabetes Care. 2009 Dec;32(12):2181-3. doi: 10.2337/dc09-0423. Epub 2009 Sep 14.
- Nanto-Salonen K, Kupila A, Simell S, Siljander H, Salonsaari T, Hekkala A, Korhonen S, Erkkola R, Sipila JI, Haavisto L, Siltala M, Tuominen J, Hakalax J, Hyoty H, Ilonen J, Veijola R, Simell T, Knip M, Simell O. Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial. Lancet. 2008 Nov 15;372(9651):1746-55. doi: 10.1016/S0140-6736(08)61309-4. Epub 2008 Sep 22.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Insulin | Protein / enzyme biologic | 1 iu/kg | Intranasal |