The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study: recruitment, intervention and follow-up

TRIGR Study Group, H K Akerblom, J Krischer, S M Virtanen, C Berseth, D Becker, J Dupré, J Ilonen, M Trucco, E Savilahti, K Koski, E Pajakkala, M Fransiscus, G Lough, B Bradley, M Koski, M Knip, Thomas Mandrup-Poulsen, Elias Arjas, Ake Lernmark, Barbara Schmidt, Jeffrey P Krischer, Hans K Akerblom, Mila Hyytinen, Mikael Knip, Katriina Koski, Matti Koski, Kristiina Merentie, Eeva Pajakkala, Antti Reunanen, Marja Salonen, Tuija Terhonen, Seija Virkkunen, David Cuthbertson, Bruce Gainer, Jeffrey P Krischer, Jamie Malloy, Lavanya Nallamshetty, Linda Shanker, Brenda Bradley, John Dupré, Gigi Lough, Debra Nielsen, Hans-Michael Dosch, William Fraser, Margaret L Lawson, Jeffrey L Mahon, Shayne P Taback, Dorothy Becker, Margaret Franciscus, Anita Nucci, Jerry Palmer, Sonja Bärlund, Eveliina Lehtonen, Minna Pekkala, Susa Sorkio, Liisa Vähätalo, Suvi M Virtanen, Ulla Uusitalo, TRIGR Study Group, H K Akerblom, J Krischer, S M Virtanen, C Berseth, D Becker, J Dupré, J Ilonen, M Trucco, E Savilahti, K Koski, E Pajakkala, M Fransiscus, G Lough, B Bradley, M Koski, M Knip, Thomas Mandrup-Poulsen, Elias Arjas, Ake Lernmark, Barbara Schmidt, Jeffrey P Krischer, Hans K Akerblom, Mila Hyytinen, Mikael Knip, Katriina Koski, Matti Koski, Kristiina Merentie, Eeva Pajakkala, Antti Reunanen, Marja Salonen, Tuija Terhonen, Seija Virkkunen, David Cuthbertson, Bruce Gainer, Jeffrey P Krischer, Jamie Malloy, Lavanya Nallamshetty, Linda Shanker, Brenda Bradley, John Dupré, Gigi Lough, Debra Nielsen, Hans-Michael Dosch, William Fraser, Margaret L Lawson, Jeffrey L Mahon, Shayne P Taback, Dorothy Becker, Margaret Franciscus, Anita Nucci, Jerry Palmer, Sonja Bärlund, Eveliina Lehtonen, Minna Pekkala, Susa Sorkio, Liisa Vähätalo, Suvi M Virtanen, Ulla Uusitalo

Abstract

Aims/hypothesis: The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study was designed to establish whether weaning to a highly hydrolysed formula in infancy subsequently reduces the risk of type 1 diabetes.

Methods: The study population comprises newborn infants who have first-degree relatives with type 1 diabetes and meet the increased risk HLA inclusion, but not exclusion criteria. The study is being performed in 15 countries in three continents. First-degree relatives of patients with type 1 diabetes were identified from diabetes clinics, diabetes registries, and from other endocrinology or obstetrics offices and websites. HLA typing was performed at birth from cord or heel stick blood, and the results sent to the study's Data Management Unit within 2 weeks for communication of eligibility to the clinical study centre. All mothers recruited were encouraged to breastfeed. The intervention lasted for 6 to 8 months, and weaning formulas based on hydrolysed casein and standard cow's milk were compared.

Results: TRIGR recruited 5,606 infants, of whom 2,160 were enrolled as eligible participants, 6% more than the target of 2,032. Of those enrolled, 80% were exposed to the study formula. The overall retention rate over the first 5 years is 87%, with protocol compliance at 94%. The randomisation code will be opened when the last recruited child turns 10 years of age, i.e. in 2017.

Conclusions/interpretation: The TRIGR experience demonstrates the feasibility and successful implementation of an international dietary intervention study. TRIGR is the first ever primary prevention trial for type 1 diabetes and, if completed successfully, will provide a definite answer to the research question.

Trial registration: ClinicalTrials.gov NCT00179777

Funding: The study was funded by the National Institute of Child Health and Development (NICHD) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) (grant numbers HD040364, HD042444 and HD051997), Canadian Institutes of Health Research, the Juvenile Diabetes Research Foundation International and the Commission of the European Communities (specific RTD programme 'Quality of Life and Management of Living Resources', contract number QLK1-2002-00372 'Diabetes Prevention'. Other funding came from the EFSD/JDRF/Novo Nordisk Focused Research Grant, Academy of Finland, Dutch Diabetes Research Foundation and Finnish Diabetes Research Foundation).

Figures

Fig. 1
Fig. 1
Trial profile for the participants in TRIGR study

References

    1. The TRIGR Study Group Study design of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) Pediatr Diabetes. 2007;8:117–137. doi: 10.1111/j.1399-5448.2007.00239.x.
    1. Åkerblom HK, Knip M, Becker D, et al. The TRIGR Trial: Testing the potential link between weaning diet and type 1 diabetes. Immunol Endocr Metab Agents Med Chem. 2007;7:251–263. doi: 10.2174/187152207780832315.
    1. Åkerblom HK, Virtanen SM, Ilonen J, et al. Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study. Diabetologia. 2005;48:829–837. doi: 10.1007/s00125-005-1733-3.
    1. Norris JM, Barriga K, Klingensmith G, et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA. 2003;290:1713–1720. doi: 10.1001/jama.290.13.1713.
    1. Ziegler AG, Schmid S, Huber D, Hummel M, Bonifacio E. Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA. 2003;290:1721–1728. doi: 10.1001/jama.290.13.1721.
    1. Siljander HTA, Salonsaari R-T, Hekkala A, et al. Role of diabetic family history in the prediabetic autoimmune process in children recruited from the general population based on HLA-associated disease risk. Diabetologia. 2010;53(Suppl. 1):S180.
    1. Savilahti E, Akerblom HK, Tainio VM, Koskimies S. Children with newly diagnosed insulin dependent diabetes mellitus have increased levels of cow’s milk antibodies. Diab Res. 1988;7:137–140.
    1. Vaarala O, Saukkonen T, Savilahti E, Klemola T, Akerblom HK. Development of immune response to cow’s milk proteins in infants receiving cow’s milk or hydrolyzed formula. J Allergy Clin Immunol. 1995;96:917–923. doi: 10.1016/S0091-6749(95)70229-6.
    1. World Health Organization . Definition, diagnosis, and classification of diabetes mellitus and its complications: report of a WHO consultation. Geneva: World Health Organization; 1999.
    1. Lorenzen T, Pociot F, Stilgren L, et al. Predictors of IDDM recurrence risk in offspring of Danish IDDM patients. Diabetologia. 1998;41:666–673. doi: 10.1007/s001250050966.
    1. Harjutsalo V, Reunanen A, Tuomilehto J. Differential transmission of type 1 diabetes from diabetic fathers and mothers to their offspring. Diabetes. 2006;55:1517–1524. doi: 10.2337/db05-1296.
    1. The EURODIAB ACE Study Group and The EURODIAB ACE Substudy 2 Study Group Familial risk of type 1 diabetes in European children. Diabetologia. 1998;41:1151–1156. doi: 10.1007/s001250051044.

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