Diabetes Mellitus, Type 1EDIANCT01735123
Early Dietary Intervention and Later Signs of Beta-Cell Autoimmunity
A study testing dietary intervention in people with Diabetes Mellitus, Type 1, run by University of Helsinki at 1 site in Finland.
Trial summary
The proposed mechanistic formula feeding study sets out to identify the mechanism(s) by which an extensively hydrolyzed casein formula is able to protect children at risk for type 1 diabetes (T1D) from beta-cell autoimmunity. Read more about this study
- Who is it for?
- Ages Up to 12 monthsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- dietary intervention
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 1 siteFinland
- Study dates
- Jan 2013to Aug 2016
- Phase
- Interventional
- 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 Up to 12 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- The infant's parents give signed consent to participate and their HLA genotype is eligible.
Who cannot join
- An older sibling of the newborn infant has been included in this study;
- 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 gestational age of the newborn infant is less than 35 weeks
- Inability of the family to take part in the study (e.g. the family had no access to the Study Center or telephone)
- 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 infant receives any infant formula other than study formula or Nutramigen at the delivery hospital
- No HLA sample has been drawn before the age of 8 days.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Early Dietary Intervention and Later Signs of Beta-Cell Autoimmunity: Potential Mechanisms
The proposed mechanistic formula feeding study sets out to identify the mechanism(s) by which an extensively hydrolyzed casein formula is able to protect children at risk for type 1 diabetes (T1D) from beta-cell autoimmunity.
Read the detailed description
Based on clinical and experimental observations the study will focus on defining the effects of two different formulas on intestinal permeability, IL (interleukin)-17 immunity, serum metabolome, and gut microflora. The study will be based on a randomized pilot intervention trial using an intention to treat statistical analysis to compare e.g. gut permeability between the two treatment groups. The investigators hypothesize that the extensively hydrolyzed casein formula decreases intestinal permeability, down-regulates IL-17 immunity and proinflammatory lysophosphatidylcholines, and stabilize Lactobacilli levels in the gut microflora when compared to the conventional cow's milk formula. The study population comprises 120 newborn infants with HLA(Human Leukocyte Antigen)-conferred susceptibility to T1D. The mothers will be encouraged to exclusively breast-feed their infants as long as possible. The timing of weaning and introduction of study formula will be left to the mother. The infants are randomized to be weaned to one of two study formulas: ( i) standard cow's milk formula and (ii) an extensively hydrolyzed casein formula. The target will be that the infant should be exposed to his/her study formula for at least 90 days before the age of 270 days. The diet of the infant will be studied with 3-day food records at the age of 3, 6, 9, and 12 months of age. To estimate the amount of breast milk received the weight of the infant will be measured just before and after each lactation. The HLA genotype will be analyzed from cord blood, and the result will be available within 10 days after birth. The family will visit the Study Center when the infant is 3, 6, 9, and 12-month-old. Blood samples will be obtained on each visit. In addition the families are asked to collect stool samples at home once a month during the study. Intestinal permeability will be assessed with the lactulose/mannitol test at the age of 3, 6, 9, and 12 months. Gut microflora will be analyzed with high-throughput, culture-independent methods and serum metabolome with established metabolomics platforms. Il-17 immunity will be studied using peripheral blood mononuclear cells. This work will generate novel knowledge of the disease process leading to overt T1D by studying potential mechanism(s) mediating the protective effect conferred by an extensively hydrolyzed casein formula against beta-cell autoimmunity. The identification of such mechanism(s) will most likely facilitate the refinement of effective preventive measures based on modifications of early infant nutrition.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- dietary intervention
- Keywords
- infant formula, diet, diabetes mellitus, type 1, autoimmunity
- Medical subject headings
- Diabetes Mellitus, Type 1, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dietary interventionDietary supplement
Also called An extensively hydrolyzed casein formula, A regular cow's milk based formula
hydrolyzed vs. nonhydrolyzed infant formula
| Study group | Role | What they receive |
|---|---|---|
| extensively hydrolyzed casein formula | Experimental | The investigators plan to randomize 60 out of 120 infants to be weaned to an extensively hydrolyzed casein formula. Recruited mothers are encouraged to breast-feed. The dietary intervention will be applied until 9 months of age. The minimum exposure time to the study formula should be 90 days. Signs of beta-cell autoimmunity, i.e. diabetes-associated autoantibodies, will be monitored in the study participants, although the study will not have sufficient power to detect statistically significant differences in the seroconversion rate between the groups due to the limited number of infants randomized. Receives: Dietary Supplement: dietary intervention |
| cow's milk based infant formula | Experimental | The investigators plan to randomize 60 out of 120 infants to be weaned to a cow's milk based infant formula. Recruited mothers are encouraged to breast-feed. The dietary intervention will be applied until 9 months of age. The minimum exposure time to the study formula should be 90 days. Signs of beta-cell autoimmunity, i.e. diabetes-associated autoantibodies, will be monitored in the study participants, although the study will not have sufficient power to detect statistically significant differences in the seroconversion rate between the groups due to the limited number of infants randomized. Receives: Dietary Supplement: dietary intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intestinal permeability will be determined at the age of 3, 6, 9 and 12 months with the lactulose/mannitol test Intestinal permeability at the age of 9 months assessed with the lactulose/mannitol test
Intestinal permeability will be determined at the age of 3, 6, 9 and 12 months with the lactulose/mannitol test
Measured: 3, 6, 9 and 12 months
Secondary outcomes (1)
Serum metabolic profile
The serum metabolic profile wil be analyzed with metabolomics at the age of 3, 6, 9, and 12 months
Measured: 3, 6, 9 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2012 (estimated)
- Study startJan 2013
- Primary completionJul 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Helsinki
- Sponsor type
- University, hospital or other
- Collaborators
- University of Turku, Finnish Institute for Health and Welfare, Tampere University Hospital
- Responsible party
- Principal investigator, Mikael Knip, University of Helsinki
- Investigators
- Mikael Knip, M.D., Principal investigator, University of Helsinki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01735123
- Sponsor's protocol ID
- 1DP3DK094338-01
- Acronym
- EDIA
- Status last verified
- Feb 2017
- First submitted
- 24 Nov 2012
- Last updated
- 27 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Salo TEI, Lalli M, Honkanen J, Ruohtula T, Mattila M, Koreasalo M, Akerlund M, Ilonen J, Vatanen T, Knip M, Hakola L, Virtanen SM. Nutrient intake, gut inflammation markers, and intestinal permeability in infants aged 6-12 months. Clin Nutr. 2026 Sep;64:106739. doi: 10.1016/j.clnu.2026.106739. Epub 2026 Jul 22.
PubMed 42526284Lalli MK, Salo TE, Hakola L, Knip M, Virtanen SM, Vatanen T. Associations between dietary fibers and gut microbiome composition in the EDIA longitudinal infant cohort. Am J Clin Nutr. 2025 Jan;121(1):83-99. doi: 10.1016/j.ajcnut.2024.11.011. Epub 2024 Nov 16.
PubMed 39551356Koivusaari K, Niinisto S, Nevalainen J, Honkanen J, Ruohtula T, Koreasalo M, Ahonen S, Akerlund M, Tapanainen H, Siljander H, Miettinen ME, Alatossava T, Ilonen J, Vaarala O, Knip M, Virtanen SM. Infant Feeding, Gut Permeability, and Gut Inflammation Markers. J Pediatr Gastroenterol Nutr. 2023 Jun 1;76(6):822-829. doi: 10.1097/MPG.0000000000003756. Epub 2023 Mar 12.
PubMed 36913717Lamichhane S, Siljander H, Salonen M, Ruohtula T, Virtanen SM, Ilonen J, Hyotylainen T, Knip M, Oresic M. Impact of Extensively Hydrolyzed Infant Formula on Circulating Lipids During Early Life. Front Nutr. 2022 May 24;9:859627. doi: 10.3389/fnut.2022.859627. eCollection 2022.
PubMed 35685890Siljander H, Jason E, Ruohtula T, Selvenius J, Koivusaari K, Salonen M, Ahonen S, Honkanen J, Ilonen J, Vaarala O, Virtanen SM, Lahdeaho ML, Knip M. Effect of Early Feeding on Intestinal Permeability and Inflammation Markers in Infants with Genetic Susceptibility to Type 1 Diabetes: A Randomized Clinical Trial. J Pediatr. 2021 Nov;238:305-311.e3. doi: 10.1016/j.jpeds.2021.07.042. Epub 2021 Jul 20.
PubMed 34293372
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Dietary Intervention and Later Signs of Beta-Cell Autoimmunity: Potential Mechanisms
- ClinicalTrials.gov ID
- NCT01735123
- Acronym / sponsor ID
- EDIA / 1DP3DK094338-01
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- infant formula, diet, diabetes mellitus, type 1, autoimmunity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- University of HelsinkiUniversity, hospital or other
- Collaborators
- University of Turku, Finnish Institute for Health and Welfare, Tampere University Hospital
- Study start
- Jan 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 28 Nov 2012 (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 proposed mechanistic formula feeding study sets out to identify the mechanism(s) by which an extensively hydrolyzed casein formula is able to protect children at risk for type 1 diabetes (T1D) from beta-cell autoimmunity.
Detailed description
Based on clinical and experimental observations the study will focus on defining the effects of two different formulas on intestinal permeability, IL (interleukin)-17 immunity, serum metabolome, and gut microflora. The study will be based on a randomized pilot intervention trial using an intention to treat statistical analysis to compare e.g. gut permeability between the two treatment groups. The investigators hypothesize that the extensively hydrolyzed casein formula decreases intestinal permeability, down-regulates IL-17 immunity and proinflammatory lysophosphatidylcholines, and stabilize Lactobacilli levels in the gut microflora when compared to the conventional cow's milk formula. The study population comprises 120 newborn infants with HLA(Human Leukocyte Antigen)-conferred susceptibility to T1D. The mothers will be encouraged to exclusively breast-feed their infants as long as possible. The timing of weaning and introduction of study formula will be left to the mother. The infants are randomized to be weaned to one of two study formulas: ( i) standard cow's milk formula and (ii) an extensively hydrolyzed casein formula. The target will be that the infant should be exposed to his/her study formula for at least 90 days before the age of 270 days. The diet of the infant will be studied with 3-day food records at the age of 3, 6, 9, and 12 months of age. To estimate the amount of breast milk received the weight of the infant will be measured just before and after each lactation. The HLA genotype will be analyzed from cord blood, and the result will be available within 10 days after birth. The family will visit the Study Center when the infant is 3, 6, 9, and 12-month-old. Blood samples will be obtained on each visit. In addition the families are asked to collect stool samples at home once a month during the study. Intestinal permeability will be assessed with the lactulose/mannitol test at the age of 3, 6, 9, and 12 months. Gut microflora will be analyzed with high-throughput, culture-independent methods and serum metabolome with established metabolomics platforms. Il-17 immunity will be studied using peripheral blood mononuclear cells. This work will generate novel knowledge of the disease process leading to overt T1D by studying potential mechanism(s) mediating the protective effect conferred by an extensively hydrolyzed casein formula against beta-cell autoimmunity. The identification of such mechanism(s) will most likely facilitate the refinement of effective preventive measures based on modifications of early infant nutrition.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| extensively hydrolyzed casein formula | Experimental | Dietary Supplement: dietary interventionThe investigators plan to randomize 60 out of 120 infants to be weaned to an extensively hydrolyzed casein formula. Recruited mothers are encouraged to breast-feed. The dietary intervention will be applied until 9 months of age. The minimum exposure time to the study formula should be 90 days. Signs of beta-cell autoimmunity, i.e. diabetes-associated autoantibodies, will be monitored in the study participants, although the study will not have sufficient power to detect statistically significant differences in the seroconversion rate between the groups due to the limited number of infants randomized. |
| cow's milk based infant formula | Experimental | Dietary Supplement: dietary interventionThe investigators plan to randomize 60 out of 120 infants to be weaned to a cow's milk based infant formula. Recruited mothers are encouraged to breast-feed. The dietary intervention will be applied until 9 months of age. The minimum exposure time to the study formula should be 90 days. Signs of beta-cell autoimmunity, i.e. diabetes-associated autoantibodies, will be monitored in the study participants, although the study will not have sufficient power to detect statistically significant differences in the seroconversion rate between the groups due to the limited number of infants randomized. |
Who may qualify
- Ages
- Up to 12 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- The infant's parents give signed consent to participate and their HLA genotype is eligible.
Key exclusion criteria (8 listed)
- An older sibling of the newborn infant has been included in this study;
- 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 gestational age of the newborn infant is less than 35 weeks
- Inability of the family to take part in the study (e.g. the family had no access to the Study Center or telephone)
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 |
|---|---|---|
| dietary interventionAlso: An extensively hydrolyzed casein formula, A regular cow's milk based formulahydrolyzed vs. nonhydrolyzed infant formula | Dietary supplement | cow's milk based infant formula, extensively hydrolyzed casein formula |
Primary outcome
Intestinal permeability will be determined at the age of 3, 6, 9 and 12 months with the lactulose/mannitol test Intestinal permeability at the age of 9 months assessed with the lactulose/mannitol test
Time frame: 3, 6, 9 and 12 months
Intestinal permeability will be determined at the age of 3, 6, 9 and 12 months with the lactulose/mannitol test
1 secondary outcome
Serum metabolic profile
Time frame: 3, 6, 9 and 12 months
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 27 Feb 2017.
- Derived from this study: PubMed 42526284Salo TEI, Lalli M, Honkanen J, Ruohtula T, Mattila M, Koreasalo M, Akerlund M, Ilonen J, Vatanen T, Knip M, Hakola L, Virtanen SM. Nutrient intake, gut inflammation markers, and intestinal permeability in infants aged 6-12 months. Clin Nutr. 2026 Sep;64:106739. doi: 10.1016/j.clnu.2026.106739. Epub 2026 Jul 22.
- Derived from this study: PubMed 39551356Lalli MK, Salo TE, Hakola L, Knip M, Virtanen SM, Vatanen T. Associations between dietary fibers and gut microbiome composition in the EDIA longitudinal infant cohort. Am J Clin Nutr. 2025 Jan;121(1):83-99. doi: 10.1016/j.ajcnut.2024.11.011. Epub 2024 Nov 16.
- Derived from this study: PubMed 36913717Koivusaari K, Niinisto S, Nevalainen J, Honkanen J, Ruohtula T, Koreasalo M, Ahonen S, Akerlund M, Tapanainen H, Siljander H, Miettinen ME, Alatossava T, Ilonen J, Vaarala O, Knip M, Virtanen SM. Infant Feeding, Gut Permeability, and Gut Inflammation Markers. J Pediatr Gastroenterol Nutr. 2023 Jun 1;76(6):822-829. doi: 10.1097/MPG.0000000000003756. Epub 2023 Mar 12.
- Derived from this study: PubMed 35685890Lamichhane S, Siljander H, Salonen M, Ruohtula T, Virtanen SM, Ilonen J, Hyotylainen T, Knip M, Oresic M. Impact of Extensively Hydrolyzed Infant Formula on Circulating Lipids During Early Life. Front Nutr. 2022 May 24;9:859627. doi: 10.3389/fnut.2022.859627. eCollection 2022.
- Derived from this study: PubMed 34293372Siljander H, Jason E, Ruohtula T, Selvenius J, Koivusaari K, Salonen M, Ahonen S, Honkanen J, Ilonen J, Vaarala O, Virtanen SM, Lahdeaho ML, Knip M. Effect of Early Feeding on Intestinal Permeability and Inflammation Markers in Infants with Genetic Susceptibility to Type 1 Diabetes: A Randomized Clinical Trial. J Pediatr. 2021 Nov;238:305-311.e3. doi: 10.1016/j.jpeds.2021.07.042. Epub 2021 Jul 20.
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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, M.D. principal investigator
University of Helsinki
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing dietary intervention in people with Diabetes Mellitus, Type 1, run by University of Helsinki at 1 site 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 1 inclusion and 8 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 27 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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?
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?
Intestinal permeability will be determined at the age of 3, 6, 9 and 12 months with the lactulose/mannitol test Intestinal permeability at the age of 9 months assessed with the lactulose/mannitol test (time frame: 3, 6, 9 and 12 months). 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 NCT01735123, which also lists 5 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 27 Feb 2017.