Diabetes Mellitus, Type 1SINT1ANCT04769037
Supplementation With B. Infantis for Mitigation of Type 1 Diabetes Autoimmunity
A study testing B. infantis in people with Diabetes Mellitus, Type 1, run by Helmholtz Zentrum München at 8 sites in 5 countries.
Trial summary
Investigator initiated, randomised, placebo-controlled, double-blind, multi-centre primary intervention study to assess whether daily administration of B. infantis EVC001 from age 7 days to 6 weeks (+14 days) until age 12 months (+ 14 days) to children with elevated genetic risk for type 1 diabetes reduces the… Read more about this study
- Who is it for?
- Ages 7 days to 6 weeksHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- B. infantis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,149 participants
- Where
- 8 sitesin 5 countries
- Study dates
- 22 Apr 2021to Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 7 days to 6 weeks
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Infants between the ages of 7 days and 6 weeks (+14 days in case of illness or COVID-19 related issues or unexpected delay in result reporting) at the time of randomisation.
- A 10% or higher genetic risk to develop multiple beta-cell autoantibodies by age 6 years:
- For infants without a first-degree family history of type 1 diabetes, high genetic risk is defined as a DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype and a genetic risk score that is in the upper 25th centile (>14.4) or a DR3/DR4-DQ8 genotype with a GRS between the upper 50th (14.0) and 25th centile and a GG genotype at the rs3763305 SNP. These represent around 1% of all newborns.
- For infants with a first-degree family history of type 1 diabetes, high genetic risk is defined as having HLA DR4 and DQ8, and none of the following protective alleles: DRB1*1501, DQB1*0503, DRB1*1303. These represent around 30% of infants with a first-degree family history of T1D.
- Written informed consent signed by the custodial parent(s).-
Who cannot join
- Any medical condition, concomitant disease or treatment that may interfere with the assessments or may jeopardize the participant's safe participation in the study, as judged by the Investigators.
- Preterm delivery < 36 weeks of gestation.
- Proven immunodeficiency.
- Any condition that could be associated with poor compliance.5. Diagnosis of diabetes at the time of recruitment
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
Germany3 sites
Universitätsklinikum Carl Gustav Carus Technische Universität Dresden
Dresden
AUF DER BULT, Kinder- und Jugendkrankenhaus
Hanover
Institute of Diabetes Research, Helmholtz Zentrum Munich, Germany, and Forschergruppe Diabetes, Technical University Munich (TUM), School of Medicine, Klinikum rechts der Isar
Munich
United Kingdom2 sites
University Department of Paediatrics, Cambridge Biomedical Campus
Cambridge
Royal Victoria Infirmary, Newcastle upon Tyne
Newcastle
Belgium1 site
University Hospitals Leuven Faculty of Medicine, Catholic University of Leuven
Leuven
About this study
Official title: "SINT1A" - Supplementation With B. Infantis for Mitigation of Type 1 Diabetes Autoimmunity - A Study of the Global Platform for the Prevention of Autoimmune Diabetes ("GPPAD")
Investigator initiated, randomised, placebo-controlled, double-blind, multi-centre primary intervention study to assess whether daily administration of B. infantis EVC001 from age 7 days to 6 weeks (+14 days) until age 12 months (+ 14 days) to children with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies in childhood.
Read the detailed description
The GPPAD-04 SINT1A study will evaluate whether early, regular supplementation with a daily dose of a probiotic can reduce the risk of developing beta-cell autoimmunity in children identified by GPPAD-02 as being genetically predisposed to developing type 1 diabetes. Children will be enrolled at age 7 days to 6 weeks (+14 days) and the study product (B. infantis EVC001 or Placebo) will be administered orally once per day from enrollment until age 12 months (+14 days).
The hypotheses is that administration of B. infantis may have a positive influence on the intestinal flora and thus have a regulating effect on the immune system. The study is designed to investigate whether pathogenic immune reactions as in type 1 diabetes but also in other diseases, such as celiac disease, can be reduced and if the disease can be prevented.
Children will be followed until age 3.5 - 6.5 years (2.5 - 5.5 years after end of treatment).
Throughout the study data will be collected by regular study visits, phone calls with the families and electronic questionaires.
Blood samples will be collected to investigate glucose, HbA1c, beta-cell autoantibodies, transglutaminase antibodies, vaccine responses, genetic susceptibility and mechanistic markers. Stool samples will be collected for further assessments such as colonization,microbiome, pH and calprotectin.
Exploratory outcomes (allergy, vaccine responses, stool microbiome, blood metabolomics, stool pH and calprotectin or site specific ancillary measurements) may be assessed or in part assessed on a portion of the participants after unblinding the study. They may not necessarily be included in the primary outcome analysis and publication.
GPPAD is committed to sharing of data in compliance with all applicable European and GPPAD Consortium Member State, Data Protection and Privacy Protection laws, rules and regulations.
Pseudonymized data of the GPPAD-04 SINT1A study will be available to the scientific community after the publication of the trial analysis, which is anticipated in 2028. The SINT1A data will be available upon request.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- B. infantis, Placebo
- Keywords
- Type 1 diabetes autoimmunity, celiac autoimmunity, respiratory infections, allergy, prevention, probiotic, B. infantis
- Medical subject headings
- Diabetes Mellitus, Type 1, Respiratory Tract Infections, Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
B. infantisDietary supplement
Activated B. infantis EVC001; Bifidobacterium longum subsp. infantis; 8 x 109 colony forming units (CFU) per day
PlaceboDietary supplement
Lactose identical in appearance and taste to the active supplement
| Study group | Role | What they receive |
|---|---|---|
| B. infantis | Active comparator | Activated B. infantis EVC001; Bifidobacterium longum subsp. infantis; 8 x 109 colony forming units (CFU) per day Receives: Dietary Supplement: B. infantis |
| Placebo | Placebo comparator | Lactose identical in appearance and taste to the active supplement Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Persistent confirmed multiple beta-cell autoantibodies
Persistent confirmed multiple beta-cell autoantibodies is defined as confirmed IAA, confirmed GADA, confirmed IA-2A, or confirmed ZnT8A in two consecutive samples, AND a confirmed second antibody from these four antibodies in one sample.
The primary outcome is the elapsed time from the random treatment assignment to the first confirmed autoantibody positive sample used in defining the persistent confirmed multiple beta-cell autoantibody positive status. Diabetes in the absence of multiple beta-cell autoantibodies is also considered as a primary outcome endpoint, and in this case, the date of diagnosis is the time of the end point.
Measured: Through study completion, up to 6.5 years
Secondary outcomes (5)
Persistent confirmed beta-cell autoantibodies
Any persistent confirmed beta-cell autoantibody, defined as at least one confirmed autoantibody in two consecutive samples, including IAA, GADA, IA-2A or ZnT8A
Measured: Through study completion, up to 6.5 years
Diabetes
Criteria for T1D onset are, as defined by the American Diabetes Association (ADA), based on glucose testing, or the presence of unequivocal hyperglycaemia with acute metabolic decompensation (diabetic ketoacidosis).
Measured: Through study completion, up to 6.5 years
Transglutaminase antibodies
Transglutaminase antibodies defined as persistent in two consecutive samples
Measured: Through study completion, up to 6.5 years
Respiratory infection rate
Respiratory infection rate in first year of life during supplementation
Measured: 1 year
Measurement of Safety parameters
Adverse Events and Serious Adverse Events will be captured until 30 days after the last administration of the food product.
Local and systemic adverse effects will be elicited by direct questioning of the participant or parent. Systemic effects will be sought by questioning about any untoward symptoms or signs, and graded as mild, moderate, severe, life-threatening or death according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.
Measured: from Baseline until 30 days after end of supplementation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2021
- Study start22 Apr 2021
- Primary completionOct 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- 1,149 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helmholtz Zentrum München
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Technical University of Munich, Kinderkrankenhaus auf der Bult, University Hospital Carl Gustav Carus, Skane University Hospital, Universitaire Ziekenhuizen KU Leuven, Medical University of Warsaw, Cambridge Biomedical Campus, Cambridge, UK, Royal Victoria Infirmary, Newcastle upon Tyne, UK
- Responsible party
- Principal investigator, Anette-Gabriele Ziegler, Helmholtz Zentrum München
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04769037
- Sponsor's protocol ID
- GPPAD-04
- Acronym
- SINT1A
- Status last verified
- Dec 2024
- First submitted
- 19 Feb 2021
- Last updated
- 13 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: GPPAD is committed to sharing of data in compliance with all applicable European and GPPAD Consortium Member State, Data Protection and Privacy Protection laws, rules and regulations. Pseudonymized data of the GPPAD-04 SINT1A study will be available to the scientific community after the publication of the trial analysis, which is anticipated in 2028. The SINT1A data will be available upon request.
Publications
Ziegler AG, Arnolds S, Kolln A, Achenbach P, Berner R, Bonifacio E, Casteels K, Elding Larsson H, Gundert M, Hasford J, Kordonouri O, Lundgren M, Oltarzewski M, Pekalski ML, Pfirrmann M, Snape MD, Szypowska A, Todd JA; GPPAD STUDY GROUP. Supplementation with Bifidobacterium longum subspecies infantis EVC001 for mitigation of type 1 diabetes autoimmunity: the GPPAD-SINT1A randomised controlled trial protocol. BMJ Open. 2021 Nov 9;11(11):e052449. doi: 10.1136/bmjopen-2021-052449.
PubMed 34753762
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "SINT1A" - Supplementation With B. Infantis for Mitigation of Type 1 Diabetes Autoimmunity - A Study of the Global Platform for the Prevention of Autoimmune Diabetes ("GPPAD")
- ClinicalTrials.gov ID
- NCT04769037
- Acronym / sponsor ID
- SINT1A / GPPAD-04
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Type 1 diabetes autoimmunity, celiac autoimmunity, respiratory infections, allergy, prevention, probiotic, B. infantis
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,149 participants (actual)
- Lead sponsor
- Helmholtz Zentrum MünchenIndustry (pharma, biotech, devices)
- Collaborators
- Technical University of Munich, Kinderkrankenhaus auf der Bult, University Hospital Carl Gustav Carus, Skane University Hospital, Universitaire Ziekenhuizen KU Leuven, Medical University of Warsaw, Cambridge Biomedical Campus, Cambridge, UK, Royal Victoria Infirmary, Newcastle upon Tyne, UK
- Study start
- 22 Apr 2021 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 24 Feb 2021 (actual)
- 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.
Investigator initiated, randomised, placebo-controlled, double-blind, multi-centre primary intervention study to assess whether daily administration of B. infantis EVC001 from age 7 days to 6 weeks (+14 days) until age 12 months (+ 14 days) to children with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies in childhood.
Detailed description
The GPPAD-04 SINT1A study will evaluate whether early, regular supplementation with a daily dose of a probiotic can reduce the risk of developing beta-cell autoimmunity in children identified by GPPAD-02 as being genetically predisposed to developing type 1 diabetes. Children will be enrolled at age 7 days to 6 weeks (+14 days) and the study product (B. infantis EVC001 or Placebo) will be administered orally once per day from enrollment until age 12 months (+14 days).
The hypotheses is that administration of B. infantis may have a positive influence on the intestinal flora and thus have a regulating effect on the immune system. The study is designed to investigate whether pathogenic immune reactions as in type 1 diabetes but also in other diseases, such as celiac disease, can be reduced and if the disease can be prevented.
Children will be followed until age 3.5 - 6.5 years (2.5 - 5.5 years after end of treatment).
Throughout the study data will be collected by regular study visits, phone calls with the families and electronic questionaires.
Blood samples will be collected to investigate glucose, HbA1c, beta-cell autoantibodies, transglutaminase antibodies, vaccine responses, genetic susceptibility and mechanistic markers. Stool samples will be collected for further assessments such as colonization,microbiome, pH and calprotectin.
Exploratory outcomes (allergy, vaccine responses, stool microbiome, blood metabolomics, stool pH and calprotectin or site specific ancillary measurements) may be assessed or in part assessed on a portion of the participants after unblinding the study. They may not necessarily be included in the primary outcome analysis and publication.
GPPAD is committed to sharing of data in compliance with all applicable European and GPPAD Consortium Member State, Data Protection and Privacy Protection laws, rules and regulations.
Pseudonymized data of the GPPAD-04 SINT1A study will be available to the scientific community after the publication of the trial analysis, which is anticipated in 2028. The SINT1A data will be available upon request.
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 |
|---|---|---|
| B. infantis | Active comparator | Dietary Supplement: B. infantisActivated B. infantis EVC001; Bifidobacterium longum subsp. infantis; 8 x 109 colony forming units (CFU) per day |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboLactose identical in appearance and taste to the active supplement |
Who may qualify
- Ages
- 7 days to 6 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Infants between the ages of 7 days and 6 weeks (+14 days in case of illness or COVID-19 related issues or unexpected delay in result reporting) at the time of randomisation.
- A 10% or higher genetic risk to develop multiple beta-cell autoantibodies by age 6 years:
- Written informed consent signed by the custodial parent(s).-
Key exclusion criteria (4 listed)
- Any medical condition, concomitant disease or treatment that may interfere with the assessments or may jeopardize the participant's safe participation in the study, as judged by the Investigators.
- Preterm delivery < 36 weeks of gestation.
- Proven immunodeficiency.
- Any condition that could be associated with poor compliance.5. Diagnosis of diabetes at the time of recruitment
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 |
|---|---|---|
| B. infantisActivated B. infantis EVC001; Bifidobacterium longum subsp. infantis; 8 x 109 colony forming units (CFU) per day | Dietary supplement | B. infantis |
| PlaceboLactose identical in appearance and taste to the active supplement | Dietary supplement | Placebo |
Primary outcome
Persistent confirmed multiple beta-cell autoantibodies
Time frame: Through study completion, up to 6.5 years
Persistent confirmed multiple beta-cell autoantibodies is defined as confirmed IAA, confirmed GADA, confirmed IA-2A, or confirmed ZnT8A in two consecutive samples, AND a confirmed second antibody from these four antibodies in one sample. The primary outcome is the elapsed time from the random treatment assignment to the first confirmed autoantibody positive sample used in defining the persistent confirmed multiple beta-cell autoantibody positive status. Diabetes in the absence of multiple beta-cell autoantibodies is also considered as a primary outcome endpoint, and in this case, the date of diagnosis is the time of the end point.
5 secondary outcomes
Persistent confirmed beta-cell autoantibodies
Time frame: Through study completion, up to 6.5 years
Diabetes
Time frame: Through study completion, up to 6.5 years
Transglutaminase antibodies
Time frame: Through study completion, up to 6.5 years
Respiratory infection rate
Time frame: 1 year
Measurement of Safety parameters
Time frame: from Baseline until 30 days after end of supplementation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.
- Derived from this study: PubMed 34753762Ziegler AG, Arnolds S, Kolln A, Achenbach P, Berner R, Bonifacio E, Casteels K, Elding Larsson H, Gundert M, Hasford J, Kordonouri O, Lundgren M, Oltarzewski M, Pekalski ML, Pfirrmann M, Snape MD, Szypowska A, Todd JA; GPPAD STUDY GROUP. Supplementation with Bifidobacterium longum subspecies infantis EVC001 for mitigation of type 1 diabetes autoimmunity: the GPPAD-SINT1A randomised controlled trial protocol. BMJ Open. 2021 Nov 9;11(11):e052449. doi: 10.1136/bmjopen-2021-052449.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. GPPAD is committed to sharing of data in compliance with all applicable European and GPPAD Consortium Member State, Data Protection and Privacy Protection laws, rules and regulations. Pseudonymized data of the GPPAD-04 SINT1A study will be available to the scientific community after the publication of the trial analysis, which is anticipated in 2028. The SINT1A data will be available upon request.
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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.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing B. infantis in people with Diabetes Mellitus, Type 1, run by Helmholtz Zentrum München at 8 sites in 5 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 5 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany, United Kingdom, Belgium, Poland, Sweden. 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?
This study is still under way. Results are not available in the source record yet.
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?
Persistent confirmed multiple beta-cell autoantibodies (time frame: Through study completion, up to 6.5 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 NCT04769037, which also lists 1 linked publication.
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 13 Dec 2024.