Nutritional Prevention Pilot Trial for Type 1 Diabetes

Type 1 Diabetes Mellitus Clinical Trial

— MIP  

Official title:

Trial to Reduce IDDM in the Genetically at Risk (TRIGR): the Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00570102
• Other study ID #: 195003
• Secondary ID: BHM4-CT96-0233
• Status: Completed
• Phase: Phase 2
• First received: December 7, 2007
• Last updated: November 27, 2012
• Start date: February 1995
• Est. completion date: January 2008

Study information

• Verified date: November 2012
• Source: Helsinki University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The overall objective of the study is to assess whether complete avoidance of cow's milk (CM) 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: January 2008
• Est. primary completion date: March 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 7 Days

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

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
• 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

Locations

Country	Name	City	State
Finland	Jorvi Hospital	Espoo
Finland	Kanta-Häme Central Hospital, Department of Pediatrics	Hämeenlinna
Finland	Helsinki University Hospital, Maternity Hospital	Helsinki
Finland	National Public Health Institute	Helsinki
Finland	University of Helsinki, Department of Obstetrics and Gynecology	Helsinki
Finland	University of Helsinki, Hospital for Children and Adolescents	Helsinki
Finland	North Karelia Central Hospital	Joensuu
Finland	Central Finland Central Hospital	Jyväskylä
Finland	Kymenlaakso Central Hospital, Department of Pediatrics	Kotka
Finland	University of Kuopio, Department of Pediatrics	Kuopio
Finland	Päijät-Häme Central Hospital	Lahti
Finland	South Karelia Central Hospital	Lappeenranta
Finland	University of Oulu, Department of Pediatrics	Oulu
Finland	Satakunta Central Hospital	Pori
Finland	South Ostrobothnia Central Hospital	Seinäjoki
Finland	Tampere University Hospital, Department of Pediatrics	Tampere
Finland	University of Turku, Department of Virology	Turku
Finland	Vaasa Central Hospital	Vaasa

Sponsors (6)

Lead Sponsor	Collaborator
Helsinki University	Academy of Finland, Diabetes Research Foundation, Finland, European Union, Juvenile Diabetes Research Foundation, Novo Nordisk A/S

Country where clinical trial is conducted

Finland, 

References & Publications (17)

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

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. — View Citation

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. — View Citation

Akerblom HK, Virtanen SM, Ilonen J, Savilahti E, Vaarala O, Reunanen A, Teramo K, Hämäläinen AM, Paronen J, Riikjärv MA, Ormisson A, Ludvigsson J, Dosch HM, Hakulinen T, Knip M; National TRIGR Study Groups. Dietary manipulation of beta cell autoimmunity i — View Citation

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 — View Citation

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. — View Citation

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

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. — View Citation

Knip M, Akerblom HK. IDDM prevention trials in progress--a critical assessment. J Pediatr Endocrinol Metab. 1998 Apr;11 Suppl 2:371-7. Review. — View Citation

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. — View Citation

Knip M, Virtanen SM, Seppä K, Ilonen J, Savilahti E, Vaarala O, Reunanen A, Teramo K, Hämäläinen AM, Paronen J, Dosch HM, Hakulinen T, Akerblom HK; Finnish TRIGR Study Group. Dietary intervention in infancy and later signs of beta-cell autoimmunity. N Eng — View Citation

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 — View Citation

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. — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

Vaarala O, Hyöty H, Akerblom HK. Environmental factors in the aetiology of childhood diabetes. Diabetes Nutr Metab. 1999 Apr;12(2):75-85. Review. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positivity for two or more diabetes-associated autoantibodies and/or clinical type 1 diabetes		10 years	No

External Links

•   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