Nutritional Prevention Pilot Trial for Type 1 Diabetes - Full Text View

Sponsors and Collaborators:	Helsinki University Academy of Finland European Union Juvenile Diabetes Research Foundation Finnish Diabetes Research Foundation Novo Nordisk
Information provided by:	Helsinki University
ClinicalTrials.gov Identifier:	NCT00570102

Purpose

The overall objective of the study is to assess whether complete avoidance of cow's milk proteins, for at least the first 6 months of life, prevents type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) in genetically susceptible children who have a mother, biological father or sibling affected by type 1 diabetes.

Condition	Intervention	Phase
Type 1 Diabetes Mellitus	Dietary Supplement: A highly hydrolyzed formula Dietary Supplement: A regular cow's milk based formula	Phase II

MedlinePlus related topics: Diabetes Diabetes Type 1 Dietary Supplements

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Trial to Reduce IDDM in the Genetically at Risk: the Pilot Study

Further study details as provided by Helsinki University:

Primary Outcome Measures:

Positivity for two or more diabetes-associated autoantibodies and/or clinical type 1 diabetes [ Time Frame: 10 years ] [ Designated as safety issue: No ]

Enrollment:	230
Study Start Date:	February 1995
Estimated Study Completion Date:	January 2008

Arms	Assigned Interventions
1: Active Comparator	Dietary Supplement: A highly hydrolyzed formula Weaning to a highly hydrolyzed formula, avoidance of all supplemental food containing cow's milk proteins and/or bovine serum albumin up to the age of 6-8 months
2: Placebo Comparator	Dietary Supplement: A regular cow's milk based formula Weaning to a regular cow's milk based formula supplemented with 20% of the highly hydrolyzed formula used in arm 1 to make the study formulas similar in smell and taste, avoidance of all supplemental food containing cow's milk proteins and/or bovine serum albumin

Detailed Description:

Among the environmental factors leading to type 1 diabetes in childhood, the most important are certain viral infections and possibly some dietary factors. Among the latter cow's milk proteins are of special interest. They have been shown to be involved in the pancreatic beta-cell lesion in animal experiments. In humans there are some indications of a role of early exposure to cow's milk proteins as a risk factor for later type 1 diabetes. The hypothesis has not been confirmed, but a randomized, controlled double-blinded intervention trial should provide a definite answer.

This study aims at assessing whether one can decrease the future incidence of beta-cell autoimmunity and/or type 1 diabetes in children who have an increased genetic risk for the disease, by administering in infancy after breast feeding until the age of 6-8 months such a formula, in which the cow's milk proteins have been hydrolyzed to smaller peptides. The children in the control group, carrying a similar increased genetic risk, will receive a conventional cow's milk based formula .

This project is a pilot multicenter trial comprising 15 hospitals in Finland.

Eligibility

Ages Eligible for Study:	up to 7 Days
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

the participant must have a mother, biological father or sibling with type 1 diabetes
the participant must carry a susceptible HLA genotype(HLA-DQB1*02 and/or DQB1*0302 without protective alleles (DQB1*0301, *0602 and *0603)

Exclusion Criteria:

no telephone
no accessibility to any of the research centers
inability of parents to understand the study and instructions
unwillingness/inability to feed the infant CM-containing food for any reason (e.g. religious, cultural reasons)
gestational age less than 36 weeks
Any severe illness such as chromosomal abnormalities, congenital malformations, respiratory failure, enzyme deficiencies of the newborn.
the newborn infant has received any cow's milk-based product prior to randomization

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00570102

Locations

Finland
University of Helsinki, Hospital for Children and Adolescents
Helsinki, Finland, FIN-00290
National Public Health Institute
Helsinki, Finland, 00300
University of Turku, Department of Virology
Turku, Finland, 20520
University of Helsinki, Department of Obstetrics and Gynecology
Helsinki, Finland, 00290
University of Oulu, Department of Pediatrics
Oulu, Finland, 90014
Tampere University Hospital, Department of Pediatrics
Tampere, Finland, 33520
University of Kuopio, Department of Pediatrics
Kuopio, Finland, 70210
Kymenlaakso Central Hospital, Department of Pediatrics
Kotka, Finland, 48210
Kanta-Häme Central Hospital, Department of Pediatrics
Hämeenlinna, Finland, 13530
Helsinki University Hospital, Maternity Hospital
Helsinki, Finland, 00610
Päijät-Häme Central Hospital
Lahti, Finland, 15850
Satakunta Central Hospital
Pori, Finland, 28500
Vaasa Central Hospital
Vaasa, Finland, 65130
South Ostrobothnia Central Hospital
Seinäjoki, Finland, 60220
Central Finland Central Hospital
Jyväskylä, Finland, 40620
North Karelia Central Hospital
Joensuu, Finland, 80210
Jorvi Hospital
Espoo, Finland, 02740
South Karelia Central Hospital
Lappeenranta, Finland, 53130

Sponsors and Collaborators

Helsinki University

Academy of Finland

European Union

Juvenile Diabetes Research Foundation

Finnish Diabetes Research Foundation

Novo Nordisk

Investigators

Principal Investigator:

Hans K Åkerlom, MD, PhD

University of Helsinki, Helsinki, Finland

More Information

The TRIGR Study proper tests the hypothesis whether weaning to a highly hydrolyzed formula reduces the cumulative incidence of beta-cell autoimmunity and clinical diabetes in subjects with increased genetic disease susceptibility This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications of Results:

Paronen J, Knip M, Savilahti E, Virtanen SM, Ilonen J, Akerblom HK, Vaarala O. Effect of cow's milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish Trial to Reduce IDDM in the Genetically at Risk Study Group. Diabetes. 2000 Oct;49(10):1657-65.

Hämäläinen AM, Ronkainen MS, Akerblom HK, Knip M. Postnatal elimination of transplacentally acquired disease-associated antibodies in infants born to families with type 1 diabetes. The Finnish TRIGR Study Group. Trial to Reduce IDDM in the Genetically at Risk. J Clin Endocrinol Metab. 2000 Nov;85(11):4249-53.

Ronkainen MS, Hämäläinen AM, Koskela P, Akerblom HK, Knip M; Finnish Trigr Study Group. Pregnancy induces nonimmunoglobulin insulin-binding activity in both maternal and cord blood serum. Clin Exp Immunol. 2001 May;124(2):190-6.

Hämäläinen AM, Savola K, Kulmala PK, Koskela P, Akerblom HK, Knip M; Finnish TRIGR Study Group. Disease-associated autoantibodies during pregnancy and at birth in families affected by type 1 diabetes. Clin Exp Immunol. 2001 Nov;126(2):230-5.

Sadeharju K, Hämäläinen AM, Knip M, Lönnrot M, Koskela P, Virtanen SM, Ilonen J, Akerblom HK, Hyöty H; Finnish TRIGR Study Group. Enterovirus infections as a risk factor for type I diabetes: virus analyses in a dietary intervention trial. Clin Exp Immunol. 2003 May;132(2):271-7.

Akerblom HK, Virtanen SM, Ilonen J, Savilahti E, Vaarala O, Reunanen A, Teramo K, Hamalainen AM, Paronen J, Riikjarv MA, Ormisson A, Ludvigsson J, Dosch HM, Hakulinen T, Knip M; National TRIGR Study Groups. Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study. Diabetologia. 2005 May;48(5):829-37. Epub 2005 Apr 19.

Tiittanen M, Paronen J, Savilahti E, Virtanen SM, Ilonen J, Knip M, Akerblom HK, Vaarala O; Finnish TRIGR Study Group. Dietary insulin as an immunogen and tolerogen. Pediatr Allergy Immunol. 2006 Nov;17(7):538-43.

Sadeharju K, Knip M, Virtanen SM, Savilahti E, Tauriainen S, Koskela P, Akerblom HK, Hyöty H; Finnish TRIGR Study Group. Maternal antibodies in breast milk protect the child from enterovirus infections. Pediatrics. 2007 May;119(5):941-6.

Other Publications:

Akerblom HK, Savilahti E, Saukkonen TT, Paganus A, Virtanen SM, Teramo K, Knip M, Ilonen J, Reijonen H, Karjalainen J, et al. The case for elimination of cow's milk in early infancy in the prevention of type 1 diabetes: the Finnish experience. Diabetes Metab Rev. 1993 Dec;9(4):269-78. Review. No abstract available.

Akerblom HK, Knip M. Putative environmental factors in Type 1 diabetes. Diabetes Metab Rev. 1998 Mar;14(1):31-67. Review.

Knip M, Akerblom HK. IDDM prevention trials in progress--a critical assessment. J Pediatr Endocrinol Metab. 1998 Apr;11 Suppl 2:371-7. Review. No abstract available.

Knip M, Akerblom HK. Environmental factors in the pathogenesis of type 1 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1999;107 Suppl 3:S93-100. Review.

Vaarala O, Hyöty H, Akerblom HK. Environmental factors in the aetiology of childhood diabetes. Diabetes Nutr Metab. 1999 Apr;12(2):75-85. Review. No abstract available.

Akerblom HK, Vaarala O, Hyöty H, Ilonen J, Knip M. Environmental factors in the etiology of type 1 diabetes. Am J Med Genet. 2002 May 30;115(1):18-29. Review.

Knip M, Akerblom HK. Early nutrition and later diabetes risk. Adv Exp Med Biol. 2005;569:142-50. Review.

Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK. Environmental triggers and determinants of type 1 diabetes. Diabetes. 2005 Dec;54 Suppl 2:S125-36. Review.

Responsible Party:	University of Helsinki ( Mikael Knip )
Study ID Numbers:	195003, BHM4-CT96-0233
Study First Received:	December 7, 2007
Last Updated:	December 7, 2007
ClinicalTrials.gov Identifier:	NCT00570102
Health Authority:	Finland: Ethics Committee

Keywords provided by Helsinki University:

dietary manipulation
infants
feasibility
Type 1 Diabetes Mellitus, Beta-cell Autoimmunity

Study placed in the following topic categories:

Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Diabetes Mellitus

Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders

Additional relevant MeSH terms:

Immune System Diseases

ClinicalTrials.gov processed this record on January 13, 2009