Intranasal Insulin for Prevention of Type 1 Diabetes

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Drug: daily intranasal administration of insulin	Phase 3

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.

Study Design

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Enrollment :	240 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double
Primary Purpose:	Prevention
Official Title:	Intranasal Insulin for Prevention of Type 1 Diabetes in Children Carrying Increased HLA-Conferred Genetic Risk
Study Start Date :	August 1997
Study Completion Date :	August 2005

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Development of clinical type 1 diabetes

Secondary Outcome Measures :

1. Number and concentration in serum of diabetes-associated autoantibodies (ICA, IAA, GADA and IA-2A)
2. Responses to intravenous glucose tolerance test
3. Possible side effects of therapy including hypoglycemia
4. Changes in serum metabolite patterns (metabolomics)

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	1 Year to 15 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Olli G Simell, MD, PhD	+358-2-313-2466	olli.simell@utu.fi
Contact: Tuula T Simell, MPH, PhD	+358-2-313-3427	tuula.simell@utu.fi

Locations

Finland
Department of Pediatrics, University of Turku	Recruiting
Turku, Finland, FI-20520
Contact: Tuula T Simell, MPH, PhD +358-2-313-3427 tuula.simell@utu.fi
Contact: Birgitta Nurmi, RN +358-2-313-2465 birgitta.nurmi@tyks.fi
Sub-Investigator: Kirsti Näntö-Salonen, MD, PhD

Sponsors and Collaborators

University of Turku

Oulu University Hospital

University of Tampere

Helsinki University

Investigators

Principal Investigator:	Olli G Simell, MD, PhD	University of Turku, Turku, Finland

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Kupila A, Sipilä 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.

Keskinen P, Korhonen S, Kupila A, Veijola R, Erkkilä 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. Epub 2002 Oct 30.

Kupila A, Keskinen P, Simell T, Erkkilä S, Arvilommi P, Korhonen S, Kimpimäki T, Sjöroos 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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Virtanen SM, Nevalainen J, Kronberg-Kippilä C, Ahonen S, Tapanainen H, Uusitalo L, Takkinen HM, Niinistö S, Ovaskainen ML, Kenward MG, Veijola R, Ilonen J, Simell O, Knip M. Food consumption and advanced β 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, Näntö-Salonen KM, Korhonen T, Kärkkäinen 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.

Näntö-Salonen K, Kupila A, Simell S, Siljander H, Salonsaari T, Hekkala A, Korhonen S, Erkkola R, Sipilä JI, Haavisto L, Siltala M, Tuominen J, Hakalax J, Hyöty 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.

ClinicalTrials.gov Identifier:	NCT00223613 History of Changes
Other Study ID Numbers:	DIPP19942014; JDRF File # 4-1999-731
First Posted:	September 22, 2005
Last Update Posted:	September 19, 2006
Last Verified:	August 2005

Keywords provided by University of Turku:

diabetes; juvenile diabetes; insulin deficiency

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases	Immune System Diseases; Insulin, Globin Zinc; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs