Diabetes Mellitus, Type 1TRIGRNCT00179777
TRIGR - Primary Prevention Study for Type 1 Diabetes in Children at Risk
A study testing Hydrolysed infant formula and Nonhydrolysed infant formula in people with Diabetes Mellitus, Type 1, run by University of Helsinki at 18 sites in 15 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 7 days
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Hydrolysed infant formula and Nonhydrolysed infant formula
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5,156 participants
- Where
- 18 sitesin 15 countries
- Study dates
- 6 May 2002to 30 Sep 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 7 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
18 sites in 15 countries.
18 sites in 15 countries
United States2 sites
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213-2583
The University of South Florida
Tampa, Florida, 33620
Italy2 sites
St. Michele Hospital
Cagliari, Sardinia, 09134
University Campus Bio-Medico of Rome
Rome, 00155
Spain2 sites
Hospital de Cruces
Barakaldo, Vizcaya, 48903
Hospital Clinico San Carlos
Madrid, 28040
Australia1 site
Children's Hospital at Westmead
Westmead, New South Wales, 2145
Czechia1 site
3rd Faculty of Medicine, Charles University, University Hospital Vinohrady
Prague, 10
About this study
Official title: 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.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Hydrolysed infant formula, Nonhydrolysed infant formula
- Keywords
- Diabetes Mellitus, Type 1, Genetic Predisposition to Disease, Infant Nutrition, Primary Prevention
- Medical subject headings
- Diabetes Mellitus, Type 1, Genetic Predisposition to Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydrolysed infant formulaDietary supplement
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.
Nonhydrolysed infant formulaDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| Hydrolysed infant formula | Experimental | Hydrolysed infant formula Receives: Dietary Supplement: Hydrolysed infant formula |
| Nonhydrolysed infant formula | Placebo comparator | Nonhydrolysed cow's milk based infant formula Receives: Dietary Supplement: Nonhydrolysed infant formula |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Type 1 Diabetes Mellitus
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.
Measured: 12 and 18 months and annually from 2 years up to 14 years
Secondary outcomes (1)
Number of Participants With Diabetes Associated Autoantibodies
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
Measured: 3, 6, 9, 12, 18 months and annually from 2 years up to 14 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study start6 May 2002
- Primary completion31 Mar 2017
- Study completion30 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5,156 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Helsinki
- Sponsor type
- University, hospital or other
- Collaborators
- United States Congress, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Canadian Institutes of Health Research (CIHR), Juvenile Diabetes Research Foundation, European Community (EC), European Foundation for the Study of Diabetes, Mead Johnson Nutrition, Academy of Finland, Diabetes Research Foundation, Finland, Dutch Diabetes Research Foundation
- Responsible party
- Principal investigator, Mikael Knip, University of Helsinki
- Investigators
- Mikael Knip, MD, Principal investigator, University of Helsinki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00179777
- Sponsor's protocol ID
- MCT-49395
- Other IDs
- U01HD040364, U01HD042444
- Acronym
- TRIGR
- Status last verified
- Jul 2021
- First submitted
- 10 Sep 2005
- Last updated
- 30 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 15838685TRIGR 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.
PubMed 17550422Åkerblom 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.
PubMed 29297078Biradar R, Kalim UU, Lonnberg T, Junttila S, Suomi T, Norman SZ, Starskaia I, Paulin N, Mikkola L, Vaarala O, Rasool O, Knip M, Elo LL, Lahesmaa R. Single-cell RNA-seq analysis of longitudinal CD4+ T cell samples reveals cell-type-specific changes during early stages of type 1 diabetes. Genome Med. 2025 Dec 29;17(1):154. doi: 10.1186/s13073-025-01574-x.
PubMed 41462339Niinisto S, Cuthbertson D, Miettinen ME, Hakola L, Nucci A, Korhonen TE, Hyoty H, Krischer JP, Vaarala O, Knip M, Savilahti E, Virtanen SM; TRIGR Investigators. High Concentrations of Immunoglobulin G Against Cow Milk Proteins and Frequency of Cow Milk Consumption Are Associated With the Development of Islet Autoimmunity and Type 1 Diabetes-The Trial to Reduce Insulin-dependent Diabetes Mellitus (IDDM) in the Genetically at Risk (TRIGR) Study. J Nutr. 2024 Aug;154(8):2493-2500. doi: 10.1016/j.tjnut.2024.06.005. Epub 2024 Jun 19.
PubMed 38906178Niinisto 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.
PubMed 35693790Nucci 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.
PubMed 33474583Pacaud 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.
PubMed 33026463Krischer 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.
PubMed 32548702Miettinen 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.
PubMed 31912198Knip 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.
PubMed 24915259Franciscus 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.
PubMed 24216218TRIGR 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.
PubMed 21153533
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TRIGR - Trial to Reduce IDDM in the Genetically at Risk
- ClinicalTrials.gov ID
- NCT00179777
- Acronym / sponsor ID
- TRIGR / MCT-49395
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Diabetes Mellitus, Type 1, Genetic Predisposition to Disease, Infant Nutrition, Primary Prevention
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,156 participants (actual)
- Lead sponsor
- University of HelsinkiUniversity, hospital or other
- Collaborators
- United States Congress, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Canadian Institutes of Health Research (CIHR), Juvenile Diabetes Research Foundation, European Community (EC), European Foundation for the Study of Diabetes, Mead Johnson Nutrition, Academy of Finland, Diabetes Research Foundation, Finland, Dutch Diabetes Research Foundation
- Study start
- 6 May 2002 (actual)
- Primary completion
- 31 Mar 2017 (actual)
- Study completion
- 30 Sep 2017 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 30 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydrolysed infant formula | Experimental | Dietary Supplement: Hydrolysed infant formulaHydrolysed infant formula |
| Nonhydrolysed infant formula | Placebo comparator | Dietary Supplement: Nonhydrolysed infant formulaNonhydrolysed cow's milk based infant formula |
Who may qualify
- Ages
- Up to 7 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydrolysed infant formulaParticipants 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. | Dietary supplement | Hydrolysed infant formula |
| Nonhydrolysed infant formulaParticipants 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. | Dietary supplement | Nonhydrolysed infant formula |
Primary outcome
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.
1 secondary outcome
Number of Participants With Diabetes Associated Autoantibodies
Time frame: 3, 6, 9, 12, 18 months and annually from 2 years up to 14 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15838685Akerblom 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.
- Background: PubMed 17550422TRIGR 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.
- BackgroundÅkerblom 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.
- Results publication: PubMed 29297078Writing 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.
- Derived from this study: PubMed 41462339Biradar R, Kalim UU, Lonnberg T, Junttila S, Suomi T, Norman SZ, Starskaia I, Paulin N, Mikkola L, Vaarala O, Rasool O, Knip M, Elo LL, Lahesmaa R. Single-cell RNA-seq analysis of longitudinal CD4+ T cell samples reveals cell-type-specific changes during early stages of type 1 diabetes. Genome Med. 2025 Dec 29;17(1):154. doi: 10.1186/s13073-025-01574-x.
- Derived from this study: PubMed 38906178Niinisto S, Cuthbertson D, Miettinen ME, Hakola L, Nucci A, Korhonen TE, Hyoty H, Krischer JP, Vaarala O, Knip M, Savilahti E, Virtanen SM; TRIGR Investigators. High Concentrations of Immunoglobulin G Against Cow Milk Proteins and Frequency of Cow Milk Consumption Are Associated With the Development of Islet Autoimmunity and Type 1 Diabetes-The Trial to Reduce Insulin-dependent Diabetes Mellitus (IDDM) in the Genetically at Risk (TRIGR) Study. J Nutr. 2024 Aug;154(8):2493-2500. doi: 10.1016/j.tjnut.2024.06.005. Epub 2024 Jun 19.
- Derived from this study: PubMed 35693790Niinisto 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.
- Derived from this study: PubMed 33474583Nucci 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.
- Derived from this study: PubMed 33026463Pacaud 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.
- Derived from this study: PubMed 32548702Krischer 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.
- Derived from this study: PubMed 31912198Miettinen 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.
- Derived from this study: PubMed 24915259Knip 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.
- TRIGR International website - Click here for more information on this study - www.TRIGR.orgLink provided by the sponsor.
- TRIGR North America website - Click here for more information on this study - www.trigrnorthamerica.orgLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mikael Knip, MD principal investigator
University of Helsinki
18 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hydrolysed infant formula and Nonhydrolysed infant formula in people with Diabetes Mellitus, Type 1, run by University of Helsinki at 18 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Italy, Spain, Australia, Canada and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Type 1 Diabetes Mellitus (time frame: 12 and 18 months and annually from 2 years up to 14 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00179777, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2021.