Clinical trial NCT00223613: Intranasal Insulin for Prevention of Type 1 Diabetes
Official title: Intranasal Insulin for Prevention of Type 1 Diabetes in Children Carrying Increased HLA-Conferred Genetic Risk
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Type 1 Diabetes
Keywords: diabetes
juvenile diabetes
insulin deficiency
Lead sponsor: University of Turku
Sponsor class: OTHER
Collaborators: name: Oulu University Hospital
name: Tampere University
name: University of Helsinki
First posted: 2005-09-22
Enrollment: 240
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed description: Children born in Turku, Oulu and Tampere university cities in Finland are screened at birth for the HLA-DQB1 and DQA1 alleles that carry increased risk to or protection from development of type 1 diabetes. Children carrying increased risk are followed at 3-month intervals until 2 years of age and then at 6-12-month intervals until,15 years of age for development of diabetes-associated autoantibodies (autoantibodies against islet cells, insulin, glutamic acid decarboxylase and IA-2 protein). 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, but serum concentrations of autoantibodies, responses to intravenous glucose tolerance test and possible side effects of therapy are also closely monitored.

Eligibility criteria: Inclusion Criteria:

* children carrying HLA-conferred genetic risk for developing type 1 diabetes
* have had at least two types of autoantibodies of ICA, IAA, GADA and IA-2A in at least two consecutive blood samples drawn at least 3 months apart
* age at least one year

Exclusion Criteria:

* severe other disease
* age above 15 years

Primary outcomes:
measure: Development of clinical type 1 diabetes
Secondary outcomes:
measure: Number and concentration in serum of diabetes-associated autoantibodies (ICA, IAA, GADA and IA-2A)
measure: Responses to intravenous glucose tolerance test
measure: Possible side effects of therapy including hypoglycemia
measure: Changes in serum metabolite patterns (metabolomics)
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Department of Pediatrics, University of Turku
Study officials:
affiliation: University of Turku, Turku, Finland
name: Olli G Simell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.