TRIGR - Primary Prevention Study for Type 1 Diabetes in Children at Risk (TRIGR)

July 9, 2021 updated by: Mikael Knip, University of Helsinki

TRIGR - Trial to Reduce IDDM in the Genetically at Risk

The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) is an international effort to conduct a primary prevention nutrition trial for type 1 (insulin-dependent) diabetes. The TRIGR study was targeted at newborns who are at genetic risk for type 1 diabetes because their mother, father and/or full sibling has type 1 diabetes. All families were encouraged to breast feed their infants for as long as possible. Prior to birth, the child was randomly assigned to receive one of two infant formulas, should formula be required prior to 8 months of age. The study determined whether weaning to a possibly protective infant formula decreases these children's chances of developing diabetes - as it does in the animal models for diabetes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The hypothesis for this study is that weaning to an extensively hydrolyzed infant formula will decrease the incidence of type 1 diabetes in subjects with risk-associated HLA genotypes and a first degree relative with type 1 diabetes, as it does in all relevant animal models for the disease.

Specific Aims:

I.a: To determine if weaning to a casein hydrolysate infant formula reduces the frequency of diabetes-predictive auto-antibodies in subjects with risk-associated HLA genotype and a first degree relative with type 1 diabetes (mother, father and/or full sibling).

I-b: To determine if weaning to a casein hydrolysate infant formula reduces the frequency of clinical diabetes in subjects with risk-associated HLA genotype and an affected first degree relative.

A secondary aim is to determine relationships between cow's milk antibodies, a measure of cow's milk exposure, and diabetes-associated auto-antibodies.

The mother of the unborn child is recruited during pregnancy. Randomization to one of two infant formulas takes place before birth (after 35 weeks gestation) or immediately after birth.

Experimental Arm: Use of extensively hydrolysed cow's milk based infant formula when needed in supplementation or substitution for breast milk through 6-8 months from birth.

Control Arm: Use of non-hydrolysed cow's milk based infant formula when needed in supplementation or substitution for breast milk through 6-8 months from birth.

All families were encouraged to breast feed their infants for as long as possible. The study infant formula was only used if exclusive breast feeding ceases before 8 months of age.

Cord blood for genotyping was obtained at birth, or failing that from a heel prick by 7 days of age. Only subjects with genotypes indicating increased genetic risk for type 1 diabetes remained in the intervention trial. All other subjects were withdrawn from the study.

All subjects were followed until the youngest subject turns age 10 years.

Study Type

Interventional

Enrollment (Actual)

5156

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Children's Hospital at Westmead
  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 5K8
        • Robarts Research Institute
  • Czechia
      • Prague, Czechia, 10
        • 3rd Faculty of Medicine, Charles University, University Hospital Vinohrady
  • Estonia
      • Tartu, Estonia, 51014
        • Tartu University Children's Hospital
  • Finland
      • Helsinki, Finland, 00029HUS
        • University of Helsinki
  • Germany
      • Hannover, Germany, 30173
        • Kinderkrankenhaus auf der Bult
  • Hungary
      • Budapest, Hungary, 1083
        • Semmelweis Medical University
  • Italy
      • Rome, Italy, 00155
        • University Campus Bio-Medico of Rome
    • Sardinia
      • Cagliari, Sardinia, Italy, 09134
        • St. Michele Hospital
  • Luxembourg
      • Luxembourg, Luxembourg, 1210
        • Centre Hospitalier de Luxembourg
  • Netherlands
      • Rotterdam, Netherlands, 3015 GJ
        • Sophia Children's Hospital
  • Poland
      • Wroclaw, Poland, 50-376
        • Medical University of Wroclaw
  • Spain
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
    • Vizcaya
      • Barakaldo, Vizcaya, Spain, 48903
        • Hospital De Cruces
  • Sweden
      • Linkoping, Sweden, S-58185
        • University of Linköping
  • Switzerland
      • Zurich, Switzerland, CH-8032
        • University Children's Hospital
  • United States
    • Florida
      • Tampa, Florida, United States, 33620
        • The University of South Florida
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213-2583
        • University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 1 week (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Biological parent and/or full (not half) sibling of the newborn infant had type 1 diabetes as defined by the World Health Organization
  • The infant's parent or legal guardians gave signed consent to participate

Exclusion Criteria:

  • An older sibling of the newborn infant had been included in the TRIGR intervention
  • Multiple gestation
  • The parents were unwilling or unable to feed the infant cow's milk based products for any reason (e.g., religious, cultural).
  • The newborn infant had a recognizable severe illness such as those due to chromosomal abnormality, congenital malformation, respiratory failure needing assisted ventilation, enzyme deficiencies, etc.
  • The gestational age of the newborn infant was less than 35 weeks.
  • The infant was older than 7 days at randomization.
  • Inability of the family to take part in the study (e.g. the family has no access to any of the Study Centers, the family has no telephone).
  • The infant had received any infant formula other than Nutramigen prior to randomization.
  • No HLA sample drawn before the age of 8 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Hydrolysed infant formula
Dietary supplement: Hydrolysed infant formula
Participants in the Hydrolysed infant formula -group received the test formula, casein hydrolysate (Nutramigen™, Mead Johnson Nutritionals), not containing antigenic CM protein, whenever breast milk is not available.
PLACEBO_COMPARATOR: Nonhydrolysed infant formula
Nonhydrolysed cow's milk based infant formula
Dietary supplement: Nonhydrolysed infant formula
Participants in the Nonydrolysed infant formula -group received the CM protein containing control formula which has an addition (20 %) of Nutramigen, whenever breast milk is not available.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Type 1 Diabetes Mellitus
Time Frame: 12 and 18 months and annually from 2 years up to 14 years
Number of participants with Type 1 diabetes mellitus assessed by (1) blood glucose and HbA1c at 12 and 18 months of age, and annually from age 2 to 10 years, and (2) oral glucose tolerance test at 6 and 10 years of age and in the final year of the study.
12 and 18 months and annually from 2 years up to 14 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Diabetes Associated Autoantibodies
Time Frame: 3, 6, 9, 12, 18 months and annually from 2 years up to 14 years
Diabetes associated autoantibodies (ICA, IAA, GADA, IA-2A) at 3, 6, 9, 12, and 18 months of age, and annually from age 2 to 10-14 years
3, 6, 9, 12, 18 months and annually from 2 years up to 14 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Helsinki

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Juvenile Diabetes Research Foundation
Canadian Institutes of Health Research (CIHR)
Mead Johnson Nutrition
Academy of Finland
European Foundation for the Study of Diabetes
Dutch Diabetes Research Foundation
Diabetes Research Foundation, Finland
US Congress
European Community (EC)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 6, 2002

Primary Completion (ACTUAL)

March 31, 2017

Study Completion (ACTUAL)

September 30, 2017

Study Registration Dates

First Submitted

September 10, 2005

First Submitted That Met QC Criteria

September 10, 2005

First Posted (ESTIMATE)

September 16, 2005

Study Record Updates

Last Update Posted (ACTUAL)

July 30, 2021

Last Update Submitted That Met QC Criteria

July 9, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCT-49395
  • U01HD040364 (NIH)
  • U01HD042444 (NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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