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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00179777




Registration number
NCT00179777
Ethics application status
Date submitted
10/09/2005
Date registered
16/09/2005
Date last updated
30/07/2021

Titles & IDs
Public title
TRIGR - Primary Prevention Study for Type 1 Diabetes in Children at Risk
Scientific title
TRIGR - Trial to Reduce IDDM in the Genetically at Risk
Secondary ID [1] 0 0
U01HD040364
Secondary ID [2] 0 0
MCT-49395
Universal Trial Number (UTN)
Trial acronym
TRIGR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 1 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Hydrolysed infant formula
Treatment: Other - Nonhydrolysed infant formula

Experimental: Hydrolysed infant formula - Hydrolysed infant formula

Placebo comparator: Nonhydrolysed infant formula - Nonhydrolysed cow's milk based infant formula


Treatment: Other: 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.

Treatment: Other: 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.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Type 1 Diabetes Mellitus
Timepoint [1] 0 0
12 and 18 months and annually from 2 years up to 14 years
Secondary outcome [1] 0 0
Number of Participants With Diabetes Associated Autoantibodies
Timepoint [1] 0 0
3, 6, 9, 12, 18 months and annually from 2 years up to 14 years

Eligibility
Key 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
Minimum age
No limit
Maximum age
7 Days
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/05/2002
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/09/2017
Sample size
Target
Accrual to date
Final
5156
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
Czechia
State/province [4] 0 0
Prague
Country [5] 0 0
Estonia
State/province [5] 0 0
Tartu
Country [6] 0 0
Finland
State/province [6] 0 0
Helsinki
Country [7] 0 0
Germany
State/province [7] 0 0
Hannover
Country [8] 0 0
Hungary
State/province [8] 0 0
Budapest
Country [9] 0 0
Italy
State/province [9] 0 0
Sardinia
Country [10] 0 0
Italy
State/province [10] 0 0
Rome
Country [11] 0 0
Luxembourg
State/province [11] 0 0
Luxembourg
Country [12] 0 0
Netherlands
State/province [12] 0 0
Rotterdam
Country [13] 0 0
Poland
State/province [13] 0 0
Wroclaw
Country [14] 0 0
Spain
State/province [14] 0 0
Vizcaya
Country [15] 0 0
Spain
State/province [15] 0 0
Madrid
Country [16] 0 0
Sweden
State/province [16] 0 0
Linkoping
Country [17] 0 0
Switzerland
State/province [17] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Other
Name
University of Helsinki
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
US Congress
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
Canadian Institutes of Health Research (CIHR)
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Juvenile Diabetes Research Foundation
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
European Community (EC)
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
European Foundation for the Study of Diabetes
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Commercial sector/industry
Name [7] 0 0
Mead Johnson Nutrition
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
Academy of Finland
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
Diabetes Research Foundation, Finland
Address [9] 0 0
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
Dutch Diabetes Research Foundation
Address [10] 0 0
Country [10] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00179777
Trial related presentations / publications
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. Erratum In: Diabetologia. 2005 Aug;48(8):1676. Riikjarv, MA [added]; Ormisson, A [added]; Ludvigsson, J [added]; Dosch, HM [added]; Hakulinen, T [added]; Knip, M [added].
TRIGR Study Group. Study design of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR). Pediatr Diabetes. 2007 Jun;8(3):117-37. doi: 10.1111/j.1399-5448.2007.00239.x.
Åkerblom HK, Knip M, Becker D, Dosch H-M, Dupré J, Ilonen J, Krischer JP and the TRIGR Study Group. The TRIGR Trial: Testing the Potential Link between Weaning Diet and Type 1 Diabetes. Immun, Endoc, Metab Agents in Med Chem 7:251-263, 2007.
Writing Group for the TRIGR Study Group; Knip M, Akerblom HK, Al Taji E, Becker D, Bruining J, Castano L, Danne T, de Beaufort C, Dosch HM, Dupre J, Fraser WD, Howard N, Ilonen J, Konrad D, Kordonouri O, Krischer JP, Lawson ML, Ludvigsson J, Madacsy L, Mahon JL, Ormisson A, Palmer JP, Pozzilli P, Savilahti E, Serrano-Rios M, Songini M, Taback S, Vaarala O, White NH, Virtanen SM, Wasikowa R. Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial. JAMA. 2018 Jan 2;319(1):38-48. doi: 10.1001/jama.2017.19826.
Niinisto S, Miettinen ME, Cuthbertson D, Honkanen J, Hakola L, Autio R, Erlund I, Arohonka P, Vuorela A, Harkonen T, Hyoty H, Krischer JP, Vaarala O, Knip M, Virtanen SM; TRIGR Investigators. Associations Between Serum Fatty Acids and Immunological Markers in Children Developing Islet Autoimmunity-The TRIGR Nested Case-Control Study. Front Immunol. 2022 May 25;13:858875. doi: 10.3389/fimmu.2022.858875. eCollection 2022.
Nucci AM, Virtanen SM, Cuthbertson D, Ludvigsson J, Einberg U, Huot C, Castano L, Aschemeier B, Becker DJ, Knip M, Krischer JP; TRIGR Investigators. Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk. Diabetologia. 2021 Apr;64(4):826-835. doi: 10.1007/s00125-020-05358-3. Epub 2021 Jan 21.
Pacaud D, Nucci AM, Cuthbertson D, Becker DJ, Virtanen SM, Ludvigsson J, Ilonen J, Knip M; TRIGR investigators. Association between family history, early growth and the risk of beta cell autoimmunity in children at risk for type 1 diabetes. Diabetologia. 2021 Jan;64(1):119-128. doi: 10.1007/s00125-020-05287-1. Epub 2020 Oct 7.
Krischer JP, Cuthbertson D, Couluris M, Knip M, Virtanen SM. Association of diabetes-related autoantibodies with the incidence of asthma, eczema and allergic rhinitis in the TRIGR randomised clinical trial. Diabetologia. 2020 Sep;63(9):1796-1807. doi: 10.1007/s00125-020-05188-3. Epub 2020 Jun 17.
Miettinen ME, Niinisto S, Erlund I, Cuthbertson D, Nucci AM, Honkanen J, Vaarala O, Hyoty H, Krischer JP, Knip M, Virtanen SM; TRIGR Investigators. Serum 25-hydroxyvitamin D concentration in childhood and risk of islet autoimmunity and type 1 diabetes: the TRIGR nested case-control ancillary study. Diabetologia. 2020 Apr;63(4):780-787. doi: 10.1007/s00125-019-05077-4. Epub 2020 Jan 7.
Knip M, Akerblom HK, Becker D, Dosch HM, Dupre J, Fraser W, Howard N, Ilonen J, Krischer JP, Kordonouri O, Lawson ML, Palmer JP, Savilahti E, Vaarala O, Virtanen SM; TRIGR Study Group. Hydrolyzed infant formula and early beta-cell autoimmunity: a randomized clinical trial. JAMA. 2014 Jun 11;311(22):2279-87. doi: 10.1001/jama.2014.5610.
Franciscus M, Nucci A, Bradley B, Suomalainen H, Greenberg E, Laforte D, Kleemola P, Hyytinen M, Salonen M, Martin MJ, Catte D, Catteau J; TRIGR Investigators. Recruitment and retention of participants for an international type 1 diabetes prevention trial: a coordinators' perspective. Clin Trials. 2014 Apr;11(2):150-8. doi: 10.1177/1740774513510070. Epub 2013 Nov 11.
TRIGR Study Group; Akerblom HK, Krischer J, Virtanen SM, Berseth C, Becker D, Dupre J, Ilonen J, Trucco M, Savilahti E, Koski K, Pajakkala E, Fransiscus M, Lough G, Bradley B, Koski M, Knip M. The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study: recruitment, intervention and follow-up. Diabetologia. 2011 Mar;54(3):627-33. doi: 10.1007/s00125-010-1964-9. Epub 2010 Dec 12. Erratum In: Diabetologia. 2011 Aug;54(8):2210.
Public notes

Contacts
Principal investigator
Name 0 0
Mikael Knip, MD
Address 0 0
University of Helsinki
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00179777