Nutritional Prevention Pilot Trial for Type 1 Diabetes

NCT ID: NCT00570102

Last Updated: 2012-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

230 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-02-28

Study Completion Date

2008-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Type 1 Diabetes Mellitus

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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A highly hydrolyzed casein formula

Group Type ACTIVE_COMPARATOR

A highly hydrolyzed formula

Intervention Type 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 conventiona cow's milk based formula

Group Type PLACEBO_COMPARATOR

A regular cow's milk based formula

Intervention Type 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

Interventions

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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

Intervention Type 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

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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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
Minimum Eligible Age

1 Day

Maximum Eligible Age

7 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Academy of Finland

OTHER

Sponsor Role collaborator

European Union

OTHER

Sponsor Role collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role collaborator

Diabetes Research Foundation, Finland

OTHER

Sponsor Role collaborator

Novo Nordisk A/S

INDUSTRY

Sponsor Role collaborator

University of Helsinki

OTHER

Sponsor Role lead

Responsible Party

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Mikael Knip

Professor of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hans K Åkerlom, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Helsinki, Helsinki, Finland

Locations

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Jorvi Hospital

Espoo, , Finland

Site Status

Kanta-Häme Central Hospital, Department of Pediatrics

Hämeenlinna, , Finland

Site Status

University of Helsinki, Department of Obstetrics and Gynecology

Helsinki, , Finland

Site Status

National Public Health Institute

Helsinki, , Finland

Site Status

Helsinki University Hospital, Maternity Hospital

Helsinki, , Finland

Site Status

University of Helsinki, Hospital for Children and Adolescents

Helsinki, , Finland

Site Status

North Karelia Central Hospital

Joensuu, , Finland

Site Status

Central Finland Central Hospital

Jyväskylä, , Finland

Site Status

Kymenlaakso Central Hospital, Department of Pediatrics

Kotka, , Finland

Site Status

University of Kuopio, Department of Pediatrics

Kuopio, , Finland

Site Status

Päijät-Häme Central Hospital

Lahti, , Finland

Site Status

South Karelia Central Hospital

Lappeenranta, , Finland

Site Status

University of Oulu, Department of Pediatrics

Oulu, , Finland

Site Status

Satakunta Central Hospital

Pori, , Finland

Site Status

South Ostrobothnia Central Hospital

Seinäjoki, , Finland

Site Status

Tampere University Hospital, Department of Pediatrics

Tampere, , Finland

Site Status

University of Turku, Department of Virology

Turku, , Finland

Site Status

Vaasa Central Hospital

Vaasa, , Finland

Site Status

Countries

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Finland

References

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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.

Reference Type BACKGROUND
PMID: 7924824 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9605629 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9642667 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10522815 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10554890 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12116173 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16137119 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16306330 (View on PubMed)

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.

Reference Type RESULT
PMID: 11016449 (View on PubMed)

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.

Reference Type RESULT
PMID: 11095462 (View on PubMed)

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.

Reference Type RESULT
PMID: 11422194 (View on PubMed)

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.

Reference Type RESULT
PMID: 11703365 (View on PubMed)

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.

Reference Type RESULT
PMID: 12699416 (View on PubMed)

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.

Reference Type RESULT
PMID: 15838685 (View on PubMed)

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.

Reference Type RESULT
PMID: 17014631 (View on PubMed)

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.

Reference Type RESULT
PMID: 17473095 (View on PubMed)

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.

Reference Type RESULT
PMID: 21067382 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28687275 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23274889 (View on PubMed)

Related Links

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http://trigr.epi.usf.edu

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

Other Identifiers

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BHM4-CT96-0233

Identifier Type: -

Identifier Source: secondary_id

195003

Identifier Type: -

Identifier Source: org_study_id