Nutritional Prevention Pilot Trial for Type 1 Diabetes

Study Overview
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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.

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

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: A highly hydrolyzed formula
* Dietary Supplement: A regular cow's milk based formula


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 7 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A highly hydrolyzed casein formula<br> | Dietary Supplement: A highly hydrolyzed formula<br>* 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<br>|
| Placebo Comparator: A conventiona cow's milk based formula<br> | Dietary Supplement: A regular cow's milk based formula<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positivity for two or more diabetes-associated autoantibodies and/or clinical type 1 diabetes |  | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dietary manipulation, infants, feasibility, Type 1 Diabetes Mellitus, Beta-cell Autoimmunity