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Nutritional Prevention Pilot Trial for Type 1 Diabetes (MIP)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00570102
First Posted: December 10, 2007
Last Update Posted: November 28, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Academy of Finland
European Union
Juvenile Diabetes Research Foundation
Diabetes Research Foundation, Finland
Novo Nordisk A/S
Information provided by (Responsible Party):
Mikael Knip, Helsinki University
  Purpose
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.

Condition Intervention Phase
Type 1 Diabetes Mellitus Dietary Supplement: A highly hydrolyzed formula Dietary Supplement: A regular cow's milk based formula Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Trial to Reduce IDDM in the Genetically at Risk (TRIGR): the Pilot Study

Resource links provided by NLM:


Further study details as provided by Mikael Knip, Helsinki University:

Primary Outcome Measures:
  • Positivity for two or more diabetes-associated autoantibodies and/or clinical type 1 diabetes [ Time Frame: 10 years ]

Enrollment: 230
Study Start Date: February 1995
Study Completion Date: January 2008
Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A highly hydrolyzed casein formula 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
Placebo Comparator: A conventiona cow's milk based formula 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

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 7 Days   (Child)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00570102


Locations
Finland
Jorvi Hospital
Espoo, Finland, 02740
University of Helsinki, Department of Obstetrics and Gynecology
Helsinki, Finland, 00290
National Public Health Institute
Helsinki, Finland, 00300
Helsinki University Hospital, Maternity Hospital
Helsinki, Finland, 00610
University of Helsinki, Hospital for Children and Adolescents
Helsinki, Finland, FIN-00290
Kanta-Häme Central Hospital, Department of Pediatrics
Hämeenlinna, Finland, 13530
North Karelia Central Hospital
Joensuu, Finland, 80210
Central Finland Central Hospital
Jyväskylä, Finland, 40620
Kymenlaakso Central Hospital, Department of Pediatrics
Kotka, Finland, 48210
University of Kuopio, Department of Pediatrics
Kuopio, Finland, 70210
Päijät-Häme Central Hospital
Lahti, Finland, 15850
South Karelia Central Hospital
Lappeenranta, Finland, 53130
University of Oulu, Department of Pediatrics
Oulu, Finland, 90014
Satakunta Central Hospital
Pori, Finland, 28500
South Ostrobothnia Central Hospital
Seinäjoki, Finland, 60220
Tampere University Hospital, Department of Pediatrics
Tampere, Finland, 33520
University of Turku, Department of Virology
Turku, Finland, 20520
Vaasa Central Hospital
Vaasa, Finland, 65130
Sponsors and Collaborators
Helsinki University
Academy of Finland
European Union
Juvenile Diabetes Research Foundation
Diabetes Research Foundation, Finland
Novo Nordisk A/S
Investigators
Principal Investigator: Hans K Åkerlom, MD, PhD University of Helsinki, Helsinki, Finland
  More Information

Additional Information:
Publications:
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, 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 in infants at increased risk of type 1 diabetes: a pilot study. Diabetologia. 2005 May;48(5):829-37. Epub 2005 Apr 19. Erratum in: Diabetologia. 2005 Aug;48(8):1676. Riikjärv, MA [added]; Ormisson, A [added]; Ludvigsson, J [added]; Dosch, HM [added]; Hakulinen, T [added]; Knip, M [added].
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.
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 Engl J Med. 2010 Nov 11;363(20):1900-8. doi: 10.1056/NEJMoa1004809.
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.
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.
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.
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mikael Knip, Professor of Pediatrics, Helsinki University
ClinicalTrials.gov Identifier: NCT00570102     History of Changes
Other Study ID Numbers: 195003
BHM4-CT96-0233
First Submitted: December 7, 2007
First Posted: December 10, 2007
Last Update Posted: November 28, 2012
Last Verified: November 2012

Keywords provided by Mikael Knip, Helsinki University:
dietary manipulation
infants
feasibility
Type 1 Diabetes Mellitus, Beta-cell Autoimmunity

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases


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