Supplementation With B. Infantis for Mitigation of Type 1 Diabetes Autoimmunity (SINT1A)

December 12, 2024 updated by: Anette-Gabriele Ziegler, Helmholtz Zentrum München

"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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1149

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Anette-G. Ziegler, Prof. Dr.
  • Phone Number: 0018 +49-(0)800-000
  • Email: contact@gppad.org

Study Contact Backup

  • Name: Peter Achenbach, Prof. Dr.
  • Phone Number: 0018 +49-(0)800-000
  • Email: contact@gppad.org

Study Locations

  • Belgium
      • Leuven, Belgium
        • University Hospitals Leuven Faculty of Medicine, Catholic University of Leuven
  • Germany
      • Dresden, Germany
        • Universitätsklinikum Carl Gustav Carus Technische Universität Dresden
      • Hannover, Germany
        • AUF DER BULT, Kinder- und Jugendkrankenhaus
      • Munich, Germany
        • Institute of Diabetes Research, Helmholtz Zentrum Munich, Germany, and Forschergruppe Diabetes, Technical University Munich (TUM), School of Medicine, Klinikum rechts der Isar
  • Poland
      • Warsaw, Poland
        • Department of Paediatrics Medical University of Warsaw
  • Sweden
      • Malmö, Sweden
        • Lund University, Skane University Hospital SUS
  • United Kingdom
      • Cambridge, United Kingdom
        • University Department of Paediatrics, Cambridge Biomedical Campus
      • Newcastle, United Kingdom
        • Royal Victoria Infirmary, Newcastle upon Tyne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 week to 1 month (Child)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. 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.

  2. A 10% or higher genetic risk to develop multiple beta-cell autoantibodies by age 6 years:

    1. 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.
    2. 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.
  3. Written informed consent signed by the custodial parent(s).-

Exclusion Criteria:

  1. 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.
  2. Preterm delivery < 36 weeks of gestation.
  3. Proven immunodeficiency.
  4. Any condition that could be associated with poor compliance.5. Diagnosis of diabetes at the time of recruitment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: B. infantis
Activated B. infantis EVC001; Bifidobacterium longum subsp. infantis; 8 x 109 colony forming units (CFU) per day
Dietary supplement: B. infantis
Activated B. infantis EVC001; Bifidobacterium longum subsp. infantis; 8 x 109 colony forming units (CFU) per day
Placebo Comparator: Placebo
Lactose identical in appearance and taste to the active supplement
Dietary supplement: Placebo
Lactose identical in appearance and taste to the active supplement

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Through study completion, up to 6.5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Persistent confirmed beta-cell autoantibodies
Time Frame: Through study completion, up to 6.5 years
Any persistent confirmed beta-cell autoantibody, defined as at least one confirmed autoantibody in two consecutive samples, including IAA, GADA, IA-2A or ZnT8A
Through study completion, up to 6.5 years
Diabetes
Time Frame: Through study completion, up to 6.5 years
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).
Through study completion, up to 6.5 years
Transglutaminase antibodies
Time Frame: Through study completion, up to 6.5 years
Transglutaminase antibodies defined as persistent in two consecutive samples
Through study completion, up to 6.5 years
Respiratory infection rate
Time Frame: 1 year
Respiratory infection rate in first year of life during supplementation
1 year
Measurement of Safety parameters
Time Frame: from Baseline until 30 days after end of supplementation

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.
from Baseline until 30 days after end of supplementation

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Allergy
Time Frame: Through study completion, up to 6.5 years
Participant's parents will be asked to complete questionnaires to obtain information about allergies every 12 months. Analyses will compare the B. infantis supplementation and placebo groups for the frequency of allergy and allergy sub-groups as defined form the yearly questionnaires.
Through study completion, up to 6.5 years
Antibody response (IgG titres) to vaccines
Time Frame: at age 6 months (rotavirus) and at age 2 years (MMR)
Information about rotavirus and MMR vaccination will be collected from parents and antibody response (IgG titers) will be measured centrally.
at age 6 months (rotavirus) and at age 2 years (MMR)
Alterations of the gut microbiome or blood metabolome
Time Frame: from baseline to age 12 months
Exploratory analyses will examine the associations between B. infantis supplementation and mouth and stool organisms (microbiome), and blood markers such as the metabolome.
from baseline to age 12 months
Stool pH
Time Frame: at age 6 months
Stool pH levels will be compared between B. infantis supplementation and placebo groups in a subset of children
at age 6 months
Stool calprotectin
Time Frame: at age 6 months
Stool calprotectin levels will be compared between B. infantis supplementation and placebo groups in a subset of children
at age 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Helmholtz Zentrum München

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Universitaire Ziekenhuizen KU Leuven
Technical University of Munich
Medical University of Warsaw
Skane University Hospital
Kinderkrankenhaus auf der Bult
University Hospital Carl Gustav Carus
Cambridge Biomedical Campus, Cambridge, UK
Royal Victoria Infirmary, Newcastle upon Tyne, UK

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 22, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 19, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 24, 2021

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 13, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 12, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GPPAD-04

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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