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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
US Congress
Canadian Institutes of Health Research (CIHR)
Juvenile Diabetes Research Foundation
European Foundation for the Study of Diabetes
European Community (EC)
Mead Johnson Nutrition
Diabetes Research Foundation, Finland
Academy of Finland
Dutch Diabetes Research Foundation
Information provided by (Responsible Party):
Margaret Lawson, Children's Hospital of Eastern Ontario
ClinicalTrials.gov Identifier:
NCT00179777
First received: September 10, 2005
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

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 is 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 are encouraged to breast feed their infants for as long as possible. Prior to birth, the child is randomly assigned to receive one of two infant formulas, should formula be required prior to 8 months of age. The study will determine 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.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Dietary Supplement: hydrolysed vs nonhydrolysed infant formula vs breast feeding
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: TRIGR - Trial to Reduce IDDM in the Genetically at Risk

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Eastern Ontario:

Primary Outcome Measures:
  • 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. [ Time Frame: 12 and 18 months and annually from 2 to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Diabetes associated islet antibodies (ICA, IAA, GADA, IA-2A) at 3, 6, 9, 12 and 18 months of age, and annually from age 2 to 10 years [ Time Frame: 3, 6, 9, 12, 18 months and annually from 2 to 10 years ] [ Designated as safety issue: No ]

Enrollment: 2032
Study Start Date: March 2002
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Intervention Details:
    Dietary Supplement: hydrolysed vs nonhydrolysed infant formula vs breast feeding
    hydrolysed vs nonhydrolysed infant formula vs breast feeding
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 case in 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 are encouraged to breast feed their infants for as long as possible. The study infant formula is only used if exclusive breast feeding ceases before 8 months of age.

Cord blood for genotyping is 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 remain in the intervention trial. All other subjects are withdrawn from the study.

All subjects will be followed for 10 years.

  Eligibility

Ages Eligible for Study:   up to 7 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • An older sibling of the newborn infant has been included in the TRIGR intervention
  • Multiple gestation
  • The parents are unwilling or unable to feed the infant cow's milk based products for any reason (e.g., religious, cultural).
  • The newborn infant has 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 is less than 35 weeks.
  • The infant is 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 has received any infant formula other than Nutramigen prior to randomization.
  • No HLA sample drawn before the age of 8 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00179777

Locations
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213-2583
Australia, New South Wales
Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145
Canada
Robarts Research Institute
London, Canada, N6A 5K8
Czech Republic
3rd Faculty of Medicine, Charles University, University Hospital Vinohrady
Prague, Czech Republic, 10
Estonia
Tartu University Children's Hospital
Tartu, Estonia, 51014
Finland
University of Helsinki
Helsinki, Finland, 00029HUS
Germany
Kinderkrankenhaus auf der Bult
Hannover, Germany, 30173
Hungary
Semmelweis Medical University
Budapest, Hungary, 1083
Italy
St. Michele Hospital
Cagliari, Sardinia, Italy, 09134
University Campus Bio-Medico of Rome
Rome, Italy, 00155
Luxembourg
Centre Hospitalier de Luxembourg
Luxembourg, Luxembourg, 1210
Netherlands
Sophia Children's Hospital
Rotterdam, Netherlands, 3015 GJ
Poland
Medical University of Wroclaw
Wroclaw, Poland, 50-376
Spain
Hospital de Cruces
Barakaldo, Vizcaya, Spain, 48903
Hospital Clinico San Carlos
Madrid, Spain, 28040
Sweden
University of Linkoping
Linkoping, Sweden, S-58185
Switzerland
University Children's Hospital
Zurich, Switzerland, CH-8032
Sponsors and Collaborators
Children's Hospital of Eastern Ontario
US Congress
Canadian Institutes of Health Research (CIHR)
Juvenile Diabetes Research Foundation
European Foundation for the Study of Diabetes
European Community (EC)
Mead Johnson Nutrition
Diabetes Research Foundation, Finland
Academy of Finland
Dutch Diabetes Research Foundation
Investigators
Principal Investigator: Hans K Akerblom, MD Helsinki University
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Margaret Lawson, Site Investigator, Children's Hospital of Eastern Ontario
ClinicalTrials.gov Identifier: NCT00179777     History of Changes
Other Study ID Numbers: MCT-49395, U01 HD40364, U01 HD42444
Study First Received: September 10, 2005
Last Updated: February 14, 2014
Health Authority: Finland: Ethics Committee

Keywords provided by Children's Hospital of Eastern Ontario:
Diabetes Mellitus, Type 1
Genetic Predisposition to Disease
Infant Nutrition
Primary Prevention

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

ClinicalTrials.gov processed this record on July 24, 2014