Nutritional Prevention Pilot Trial for Type 1 Diabetes

NCT00570102 | Completed Phase 2

• 2 other identifiers: 195003BHM4-CT96-0233
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 18

Brief 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.

Conditions

Type 1 Diabetes Mellitus

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Positivity for two or more diabetes-associated autoantibodies and/or clinical type 1 diabetes

  10 years

Study Arms (2)

A highly hydrolyzed casein formula

ACTIVE COMPARATOR

Dietary Supplement: A highly hydrolyzed formula

A conventiona cow's milk based formula

PLACEBO COMPARATOR

Dietary Supplement: A regular cow's milk based formula

Interventions

A highly hydrolyzed formula DIETARY_SUPPLEMENT

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 highly hydrolyzed casein formula

A regular cow's milk based formula DIETARY_SUPPLEMENT

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

A conventiona cow's milk based formula

Eligibility Criteria

• Age: 1 Day - 7 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Helsinki: lead
• Academy of Finland: collaborator
• European Union: collaborator
• Juvenile Diabetes Research Foundation: collaborator
• Diabetes Research Foundation, Finland: collaborator
• Novo Nordisk A/S: collaborator

Study Sites (18)

Jorvi Hospital

Espoo, 02740, Finland

Location

Kanta-Häme Central Hospital, Department of Pediatrics

Hämeenlinna, 13530, Finland

Location

University of Helsinki, Department of Obstetrics and Gynecology

Helsinki, 00290, Finland

Location

National Public Health Institute

Helsinki, 00300, Finland

Location

Helsinki University Hospital, Maternity Hospital

Helsinki, 00610, Finland

Location

University of Helsinki, Hospital for Children and Adolescents

Helsinki, FIN-00290, Finland

Location

North Karelia Central Hospital

Joensuu, 80210, Finland

Location

Central Finland Central Hospital

Jyväskylä, 40620, Finland

Location

Kymenlaakso Central Hospital, Department of Pediatrics

Kotka, 48210, Finland

Location

University of Kuopio, Department of Pediatrics

Kuopio, 70210, Finland

Location

Päijät-Häme Central Hospital

Lahti, 15850, Finland

Location

South Karelia Central Hospital

Lappeenranta, 53130, Finland

Location

University of Oulu, Department of Pediatrics

Oulu, 90014, Finland

Location

Satakunta Central Hospital

Pori, 28500, Finland

Location

South Ostrobothnia Central Hospital

Seinäjoki, 60220, Finland

Location

Tampere University Hospital, Department of Pediatrics

Tampere, 33520, Finland

Location

University of Turku, Department of Virology

Turku, 20520, Finland

Location

Vaasa Central Hospital

Vaasa, 65130, Finland

Location

Related Publications (19)

• 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. doi: 10.1002/dmr.5610090407. No abstract available.

  PMID: 7924824 BACKGROUND

• Akerblom HK, Knip M. Putative environmental factors in Type 1 diabetes. Diabetes Metab Rev. 1998 Mar;14(1):31-67. doi: 10.1002/(sici)1099-0895(199803)14:13.0.co;2-a.

  PMID: 9605629 BACKGROUND

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

  PMID: 9642667 BACKGROUND

• Knip M, Akerblom HK. Environmental factors in the pathogenesis of type 1 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1999;107 Suppl 3:S93-100. doi: 10.1055/s-0029-1212160.

  PMID: 10522815 BACKGROUND

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

  PMID: 10554890 BACKGROUND

• Akerblom HK, Vaarala O, Hyoty 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. doi: 10.1002/ajmg.10340.

  PMID: 12116173 BACKGROUND

• Knip M, Akerblom HK. Early nutrition and later diabetes risk. Adv Exp Med Biol. 2005;569:142-50. doi: 10.1007/1-4020-3535-7_21.

  PMID: 16137119 BACKGROUND

• Knip M, Veijola R, Virtanen SM, Hyoty H, Vaarala O, Akerblom HK. Environmental triggers and determinants of type 1 diabetes. Diabetes. 2005 Dec;54 Suppl 2:S125-36. doi: 10.2337/diabetes.54.suppl_2.s125.

  PMID: 16306330 BACKGROUND

• 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. doi: 10.2337/diabetes.49.10.1657.

  PMID: 11016449 RESULT

• Hamalainen 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. doi: 10.1210/jcem.85.11.6987.

  PMID: 11095462 RESULT

• Ronkainen MS, Hamalainen 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. doi: 10.1046/j.1365-2249.2001.01506.x.

  PMID: 11422194 RESULT

• Hamalainen 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. doi: 10.1046/j.1365-2249.2001.01676.x.

  PMID: 11703365 RESULT

• Sadeharju K, Hamalainen AM, Knip M, Lonnrot M, Koskela P, Virtanen SM, Ilonen J, Akerblom HK, Hyoty 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. doi: 10.1046/j.1365-2249.2003.02147.x.

  PMID: 12699416 RESULT

• 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. doi: 10.1007/s00125-005-1733-3. Epub 2005 Apr 19.

  PMID: 15838685 RESULT

• 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. doi: 10.1111/j.1399-3038.2006.00447.x.

  PMID: 17014631 RESULT

• Sadeharju K, Knip M, Virtanen SM, Savilahti E, Tauriainen S, Koskela P, Akerblom HK, Hyoty H; Finnish TRIGR Study Group. Maternal antibodies in breast milk protect the child from enterovirus infections. Pediatrics. 2007 May;119(5):941-6. doi: 10.1542/peds.2006-0780.

  PMID: 17473095 RESULT

• Knip M, Virtanen SM, Seppa K, Ilonen J, Savilahti E, Vaarala O, Reunanen A, Teramo K, Hamalainen 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 Engl J Med. 2010 Nov 11;363(20):1900-8. doi: 10.1056/NEJMoa1004809.

  PMID: 21067382 RESULT

• Hyytinen M, Savilahti E, Virtanen SM, Harkonen T, Ilonen J, Luopajarvi K, Uibo R, Vaarala O, Akerblom HK, Knip M; Finnish TRIGR Pilot Study Group. Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial. Gastroenterology. 2017 Oct;153(4):961-970.e3. doi: 10.1053/j.gastro.2017.06.049. Epub 2017 Jul 5.

  PMID: 28687275 DERIVED

• de Goffau MC, Luopajarvi K, Knip M, Ilonen J, Ruohtula T, Harkonen T, Orivuori L, Hakala S, Welling GW, Harmsen HJ, Vaarala O. Fecal microbiota composition differs between children with beta-cell autoimmunity and those without. Diabetes. 2013 Apr;62(4):1238-44. doi: 10.2337/db12-0526. Epub 2012 Dec 28.

  PMID: 23274889 DERIVED

Related 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

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Hans K Åkerlom, MD, PhD

  University of Helsinki, Helsinki, Finland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: December 7, 2007
• First Posted: December 10, 2007
• Study Start: February 1, 1995
• Primary Completion: March 1, 2004
• Study Completion: January 1, 2008
• Last Updated: November 28, 2012

Record last verified: 2012-11

Locations

FI (18)