Type 1 Diabetes MellitusPhase 2MIPNCT00570102
Nutritional Prevention Pilot Trial for Type 1 Diabetes
A Phase 2 study testing A highly hydrolyzed formula and A regular cow's milk based formula in people with Type 1 Diabetes Mellitus, run by University of Helsinki at 18 sites in Finland.
Trial summary
The overall objective of the study is to assess whether complete avoidance of cow's milk (CM) proteins, for at least the first 6 months of life, prevents type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) in genetically susceptible children who have a mother, biological father or sibling affected by type 1… Read more about this study
- Who is it for?
- Ages 1 day to 7 daysHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- A highly hydrolyzed formula and A regular cow's milk based formula
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 230 participants
- Where
- 18 sitesFinland
- Study dates
- Feb 1995to Jan 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 1 day to 7 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- the participant must have a mother, biological father or sibling with type 1 diabetes
- the participant must carry a susceptible HLA genotype(HLA-DQB1*02 and/or DQB1*0302 without protective alleles (DQB1*0301, *0602 and *0603)
Who cannot join
- no telephone
- no accessibility to any of the research centers
- inability of parents to understand the study and instructions
- unwillingness/inability to feed the infant CM-containing food for any reason (e.g. religious, cultural reasons)
- gestational age less than 36 weeks
- Any severe illness such as chromosomal abnormalities, congenital malformations, respiratory failure, enzyme deficiencies of the newborn.
- the newborn infant has received any cow's milk-based product prior to randomization
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
Finland18 sites
Jorvi Hospital
Espoo, 02740
Kanta-Häme Central Hospital, Department of Pediatrics
Hämeenlinna, 13530
University of Helsinki, Department of Obstetrics and Gynecology
Helsinki, 00290
National Public Health Institute
Helsinki, 00300
Helsinki University Hospital, Maternity Hospital
Helsinki, 00610
University of Helsinki, Hospital for Children and Adolescents
Helsinki, FIN-00290
North Karelia Central Hospital
Joensuu, 80210
Central Finland Central Hospital
Jyväskylä, 40620
Kymenlaakso Central Hospital, Department of Pediatrics
Kotka, 48210
University of Kuopio, Department of Pediatrics
Kuopio, 70210
Päijät-Häme Central Hospital
Lahti, 15850
South Karelia Central Hospital
Lappeenranta, 53130
University of Oulu, Department of Pediatrics
Oulu, 90014
Satakunta Central Hospital
Pori, 28500
South Ostrobothnia Central Hospital
Seinäjoki, 60220
Tampere University Hospital, Department of Pediatrics
Tampere, 33520
University of Turku, Department of Virology
Turku, 20520
Vaasa Central Hospital
Vaasa, 65130
About this study
Official title: Trial to Reduce IDDM in the Genetically at Risk (TRIGR): the Pilot Study
The overall objective of the study is to assess whether complete avoidance of cow's milk (CM) proteins, for at least the first 6 months of life, prevents type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) in genetically susceptible children who have a mother, biological father or sibling affected by type 1 diabetes.
Read the detailed description
Among the environmental factors leading to type 1 diabetes in childhood, the most important are certain viral infections and possibly some dietary factors. Among the latter cow's milk proteins are of special interest. They have been shown to be involved in the pancreatic beta-cell lesion in animal experiments. In humans there are some indications of a role of early exposure to cow's milk proteins as a risk factor for later type 1 diabetes. The hypothesis has not been confirmed, but a randomized, controlled double-blinded intervention trial should provide a definite answer.
This study aims at assessing whether one can decrease the future incidence of beta-cell autoimmunity and/or type 1 diabetes in children who have an increased genetic risk for the disease, by administering in infancy after breast feeding until the age of 6-8 months such a formula, in which the cow's milk proteins have been hydrolyzed to smaller peptides. The children in the control group, carrying a similar increased genetic risk, will receive a conventional cow's milk based formula .
This project is a pilot multicenter trial comprising 15 hospitals in Finland.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- A highly hydrolyzed formula, A regular cow's milk based formula
- Keywords
- dietary manipulation, infants, feasibility, Type 1 Diabetes Mellitus, Beta-cell Autoimmunity
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A highly hydrolyzed formulaDietary supplement
Weaning to a highly hydrolyzed formula, avoidance of all supplemental food containing cow's milk proteins and/or bovine serum albumin up to the age of 6-8 months
A regular cow's milk based formulaDietary supplement
Weaning to a regular cow's milk based formula supplemented with 20% of the highly hydrolyzed formula used in arm 1 to make the study formulas similar in smell and taste, avoidance of all supplemental food containing cow's milk proteins and/or bovine serum albumin
| Study group | Role | What they receive |
|---|---|---|
| A highly hydrolyzed casein formula | Active comparator | Not described Receives: Dietary Supplement: A highly hydrolyzed formula |
| A conventiona cow's milk based formula | Placebo comparator | Not described Receives: Dietary Supplement: A regular cow's milk based formula |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positivity for two or more diabetes-associated autoantibodies and/or clinical type 1 diabetes
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2007 (estimated)
- Study startFeb 1995
- Primary completionMar 2004
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Helsinki
- Sponsor type
- University, hospital or other
- Collaborators
- Academy of Finland, European Union, Juvenile Diabetes Research Foundation, Diabetes Research Foundation, Finland, Novo Nordisk A/S
- Responsible party
- Principal investigator, Mikael Knip, University of Helsinki
- Investigators
- Hans K Åkerlom, MD, PhD, Principal investigator, University of Helsinki, Helsinki, Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00570102
- Sponsor's protocol ID
- 195003
- Other IDs
- BHM4-CT96-0233
- Acronym
- MIP
- Status last verified
- Nov 2012
- First submitted
- 7 Dec 2007
- Last updated
- 28 Nov 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Akerblom HK, Savilahti E, Saukkonen TT, Paganus A, Virtanen SM, Teramo K, Knip M, Ilonen J, Reijonen H, Karjalainen J, et al. The case for elimination of cow's milk in early infancy in the prevention of type 1 diabetes: the Finnish experience. Diabetes Metab Rev. 1993 Dec;9(4):269-78. doi: 10.1002/dmr.5610090407. No abstract available.
PubMed 7924824Akerblom HK, Knip M. Putative environmental factors in Type 1 diabetes. Diabetes Metab Rev. 1998 Mar;14(1):31-67. doi: 10.1002/(sici)1099-0895(199803)14:13.0.co;2-a.
PubMed 9605629Knip M, Akerblom HK. IDDM prevention trials in progress--a critical assessment. J Pediatr Endocrinol Metab. 1998 Apr;11 Suppl 2:371-7. No abstract available.
PubMed 9642667Knip M, Akerblom HK. Environmental factors in the pathogenesis of type 1 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1999;107 Suppl 3:S93-100. doi: 10.1055/s-0029-1212160.
PubMed 10522815Vaarala O, Hyoty H, Akerblom HK. Environmental factors in the aetiology of childhood diabetes. Diabetes Nutr Metab. 1999 Apr;12(2):75-85. No abstract available.
PubMed 10554890Akerblom HK, Vaarala O, Hyoty H, Ilonen J, Knip M. Environmental factors in the etiology of type 1 diabetes. Am J Med Genet. 2002 May 30;115(1):18-29. doi: 10.1002/ajmg.10340.
PubMed 12116173Knip M, Akerblom HK. Early nutrition and later diabetes risk. Adv Exp Med Biol. 2005;569:142-50. doi: 10.1007/1-4020-3535-7_21.
PubMed 16137119Knip M, Veijola R, Virtanen SM, Hyoty H, Vaarala O, Akerblom HK. Environmental triggers and determinants of type 1 diabetes. Diabetes. 2005 Dec;54 Suppl 2:S125-36. doi: 10.2337/diabetes.54.suppl_2.s125.
PubMed 16306330Paronen J, Knip M, Savilahti E, Virtanen SM, Ilonen J, Akerblom HK, Vaarala O. Effect of cow's milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish Trial to Reduce IDDM in the Genetically at Risk Study Group. Diabetes. 2000 Oct;49(10):1657-65. doi: 10.2337/diabetes.49.10.1657.
PubMed 11016449Hamalainen AM, Ronkainen MS, Akerblom HK, Knip M. Postnatal elimination of transplacentally acquired disease-associated antibodies in infants born to families with type 1 diabetes. The Finnish TRIGR Study Group. Trial to Reduce IDDM in the Genetically at Risk. J Clin Endocrinol Metab. 2000 Nov;85(11):4249-53. doi: 10.1210/jcem.85.11.6987.
PubMed 11095462Ronkainen MS, Hamalainen AM, Koskela P, Akerblom HK, Knip M; Finnish Trigr Study Group. Pregnancy induces nonimmunoglobulin insulin-binding activity in both maternal and cord blood serum. Clin Exp Immunol. 2001 May;124(2):190-6. doi: 10.1046/j.1365-2249.2001.01506.x.
PubMed 11422194Hamalainen AM, Savola K, Kulmala PK, Koskela P, Akerblom HK, Knip M; Finnish TRIGR Study Group. Disease-associated autoantibodies during pregnancy and at birth in families affected by type 1 diabetes. Clin Exp Immunol. 2001 Nov;126(2):230-5. doi: 10.1046/j.1365-2249.2001.01676.x.
PubMed 11703365Sadeharju K, Hamalainen AM, Knip M, Lonnrot M, Koskela P, Virtanen SM, Ilonen J, Akerblom HK, Hyoty H; Finnish TRIGR Study Group. Enterovirus infections as a risk factor for type I diabetes: virus analyses in a dietary intervention trial. Clin Exp Immunol. 2003 May;132(2):271-7. doi: 10.1046/j.1365-2249.2003.02147.x.
PubMed 12699416Akerblom 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 15838685Tiittanen M, Paronen J, Savilahti E, Virtanen SM, Ilonen J, Knip M, Akerblom HK, Vaarala O; Finnish TRIGR Study Group. Dietary insulin as an immunogen and tolerogen. Pediatr Allergy Immunol. 2006 Nov;17(7):538-43. doi: 10.1111/j.1399-3038.2006.00447.x.
PubMed 17014631
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial to Reduce IDDM in the Genetically at Risk (TRIGR): the Pilot Study
- ClinicalTrials.gov ID
- NCT00570102
- Acronym / sponsor ID
- MIP / 195003
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- dietary manipulation, infants, feasibility, Type 1 Diabetes Mellitus, Beta-cell Autoimmunity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 230 participants (actual)
- Lead sponsor
- University of HelsinkiUniversity, hospital or other
- Collaborators
- Academy of Finland, European Union, Juvenile Diabetes Research Foundation, Diabetes Research Foundation, Finland, Novo Nordisk A/S
- Study start
- Feb 1995
- Primary completion
- Mar 2004 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 10 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overall objective of the study is to assess whether complete avoidance of cow's milk (CM) proteins, for at least the first 6 months of life, prevents type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) in genetically susceptible children who have a mother, biological father or sibling affected by type 1 diabetes.
Detailed description
Among the environmental factors leading to type 1 diabetes in childhood, the most important are certain viral infections and possibly some dietary factors. Among the latter cow's milk proteins are of special interest. They have been shown to be involved in the pancreatic beta-cell lesion in animal experiments. In humans there are some indications of a role of early exposure to cow's milk proteins as a risk factor for later type 1 diabetes. The hypothesis has not been confirmed, but a randomized, controlled double-blinded intervention trial should provide a definite answer.
This study aims at assessing whether one can decrease the future incidence of beta-cell autoimmunity and/or type 1 diabetes in children who have an increased genetic risk for the disease, by administering in infancy after breast feeding until the age of 6-8 months such a formula, in which the cow's milk proteins have been hydrolyzed to smaller peptides. The children in the control group, carrying a similar increased genetic risk, will receive a conventional cow's milk based formula .
This project is a pilot multicenter trial comprising 15 hospitals in Finland.
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 |
|---|---|---|
| A highly hydrolyzed casein formula | Active comparator | Dietary Supplement: A highly hydrolyzed formula |
| A conventiona cow's milk based formula | Placebo comparator | Dietary Supplement: A regular cow's milk based formula |
Who may qualify
- Ages
- 1 day to 7 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- the participant must have a mother, biological father or sibling with type 1 diabetes
- the participant must carry a susceptible HLA genotype(HLA-DQB1*02 and/or DQB1*0302 without protective alleles (DQB1*0301, *0602 and *0603)
Key exclusion criteria (7 listed)
- no telephone
- no accessibility to any of the research centers
- inability of parents to understand the study and instructions
- unwillingness/inability to feed the infant CM-containing food for any reason (e.g. religious, cultural reasons)
- gestational age less than 36 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 |
|---|---|---|
| A highly hydrolyzed formulaWeaning to a highly hydrolyzed formula, avoidance of all supplemental food containing cow's milk proteins and/or bovine serum albumin up to the age of 6-8 months | Dietary supplement | A highly hydrolyzed casein formula |
| A regular cow's milk based formulaWeaning to a regular cow's milk based formula supplemented with 20% of the highly hydrolyzed formula used in arm 1 to make the study formulas similar in smell and taste, avoidance of all supplemental food containing cow's milk proteins and/or bovine serum albumin | Dietary supplement | A conventiona cow's milk based formula |
Primary outcome
Positivity for two or more diabetes-associated autoantibodies and/or clinical type 1 diabetes
Time frame: 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2012.
- Background: PubMed 7924824Akerblom HK, Savilahti E, Saukkonen TT, Paganus A, Virtanen SM, Teramo K, Knip M, Ilonen J, Reijonen H, Karjalainen J, et al. The case for elimination of cow's milk in early infancy in the prevention of type 1 diabetes: the Finnish experience. Diabetes Metab Rev. 1993 Dec;9(4):269-78. doi: 10.1002/dmr.5610090407. No abstract available.
- Background: PubMed 9605629Akerblom HK, Knip M. Putative environmental factors in Type 1 diabetes. Diabetes Metab Rev. 1998 Mar;14(1):31-67. doi: 10.1002/(sici)1099-0895(199803)14:13.0.co;2-a.
- Background: PubMed 9642667Knip M, Akerblom HK. IDDM prevention trials in progress--a critical assessment. J Pediatr Endocrinol Metab. 1998 Apr;11 Suppl 2:371-7. No abstract available.
- Background: PubMed 10522815Knip M, Akerblom HK. Environmental factors in the pathogenesis of type 1 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1999;107 Suppl 3:S93-100. doi: 10.1055/s-0029-1212160.
- Background: PubMed 10554890Vaarala O, Hyoty H, Akerblom HK. Environmental factors in the aetiology of childhood diabetes. Diabetes Nutr Metab. 1999 Apr;12(2):75-85. No abstract available.
- Background: PubMed 12116173Akerblom HK, Vaarala O, Hyoty H, Ilonen J, Knip M. Environmental factors in the etiology of type 1 diabetes. Am J Med Genet. 2002 May 30;115(1):18-29. doi: 10.1002/ajmg.10340.
- Background: PubMed 16137119Knip M, Akerblom HK. Early nutrition and later diabetes risk. Adv Exp Med Biol. 2005;569:142-50. doi: 10.1007/1-4020-3535-7_21.
- Background: PubMed 16306330Knip M, Veijola R, Virtanen SM, Hyoty H, Vaarala O, Akerblom HK. Environmental triggers and determinants of type 1 diabetes. Diabetes. 2005 Dec;54 Suppl 2:S125-36. doi: 10.2337/diabetes.54.suppl_2.s125.
- Results publication: PubMed 11016449Paronen J, Knip M, Savilahti E, Virtanen SM, Ilonen J, Akerblom HK, Vaarala O. Effect of cow's milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish Trial to Reduce IDDM in the Genetically at Risk Study Group. Diabetes. 2000 Oct;49(10):1657-65. doi: 10.2337/diabetes.49.10.1657.
- Results publication: PubMed 11095462Hamalainen AM, Ronkainen MS, Akerblom HK, Knip M. Postnatal elimination of transplacentally acquired disease-associated antibodies in infants born to families with type 1 diabetes. The Finnish TRIGR Study Group. Trial to Reduce IDDM in the Genetically at Risk. J Clin Endocrinol Metab. 2000 Nov;85(11):4249-53. doi: 10.1210/jcem.85.11.6987.
- Results publication: PubMed 11422194Ronkainen MS, Hamalainen AM, Koskela P, Akerblom HK, Knip M; Finnish Trigr Study Group. Pregnancy induces nonimmunoglobulin insulin-binding activity in both maternal and cord blood serum. Clin Exp Immunol. 2001 May;124(2):190-6. doi: 10.1046/j.1365-2249.2001.01506.x.
- Results publication: PubMed 11703365Hamalainen AM, Savola K, Kulmala PK, Koskela P, Akerblom HK, Knip M; Finnish TRIGR Study Group. Disease-associated autoantibodies during pregnancy and at birth in families affected by type 1 diabetes. Clin Exp Immunol. 2001 Nov;126(2):230-5. doi: 10.1046/j.1365-2249.2001.01676.x.
- The TRIGR Study proper tests the hypothesis whether weaning to a highly hydrolyzed formula reduces the cumulative incidence of beta-cell autoimmunity and clinical diabetes in subjects with increased genetic disease susceptibilityLink provided by the sponsor.
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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.
Hans K Åkerlom, MD, PhD principal investigator
University of Helsinki, Helsinki, Finland
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing A highly hydrolyzed formula and A regular cow's milk based formula in people with Type 1 Diabetes Mellitus, run by University of Helsinki at 18 sites in Finland.
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 7 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 28 Nov 2012. 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 Finland. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Positivity for two or more diabetes-associated autoantibodies and/or clinical type 1 diabetes (time frame: 10 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 NCT00570102, which also lists 19 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 28 Nov 2012.