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

NCT ID: NCT04769037

Last Updated: 2024-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

1149 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-22

Study Completion Date

2027-10-31

Brief Summary

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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

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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

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Diabetes Mellitus, Type 1

Keywords

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Type 1 diabetes autoimmunity celiac autoimmunity respiratory infections allergy prevention probiotic B. infantis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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B. infantis

Activated B. infantis EVC001; Bifidobacterium longum subsp. infantis; 8 x 109 colony forming units (CFU) per day

Group Type ACTIVE_COMPARATOR

B. infantis

Intervention Type DIETARY_SUPPLEMENT

Activated B. infantis EVC001; Bifidobacterium longum subsp. infantis; 8 x 109 colony forming units (CFU) per day

Placebo

Lactose identical in appearance and taste to the active supplement

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DIETARY_SUPPLEMENT

Lactose identical in appearance and taste to the active supplement

Interventions

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B. infantis

Activated B. infantis EVC001; Bifidobacterium longum subsp. infantis; 8 x 109 colony forming units (CFU) per day

Intervention Type DIETARY_SUPPLEMENT

Placebo

Lactose identical in appearance and taste to the active supplement

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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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
Minimum Eligible Age

7 Days

Maximum Eligible Age

6 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Technical University of Munich

OTHER

Sponsor Role collaborator

Kinderkrankenhaus auf der Bult

OTHER

Sponsor Role collaborator

University Hospital Carl Gustav Carus

OTHER

Sponsor Role collaborator

Skane University Hospital

OTHER

Sponsor Role collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role collaborator

Medical University of Warsaw

OTHER

Sponsor Role collaborator

Cambridge Biomedical Campus, Cambridge, UK

UNKNOWN

Sponsor Role collaborator

Royal Victoria Infirmary, Newcastle upon Tyne, UK

UNKNOWN

Sponsor Role collaborator

Helmholtz Zentrum München

INDUSTRY

Sponsor Role lead

Responsible Party

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Anette-Gabriele Ziegler

Director - Institute of Diabetes Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University Hospitals Leuven Faculty of Medicine, Catholic University of Leuven

Leuven, , Belgium

Site Status

Universitätsklinikum Carl Gustav Carus Technische Universität Dresden

Dresden, , Germany

Site Status

AUF DER BULT, Kinder- und Jugendkrankenhaus

Hanover, , Germany

Site Status

Institute of Diabetes Research, Helmholtz Zentrum Munich, Germany, and Forschergruppe Diabetes, Technical University Munich (TUM), School of Medicine, Klinikum rechts der Isar

Munich, , Germany

Site Status

Department of Paediatrics Medical University of Warsaw

Warsaw, , Poland

Site Status

Lund University, Skane University Hospital SUS

Malmo, , Sweden

Site Status

University Department of Paediatrics, Cambridge Biomedical Campus

Cambridge, , United Kingdom

Site Status

Royal Victoria Infirmary, Newcastle upon Tyne

Newcastle, , United Kingdom

Site Status

Countries

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Belgium Germany Poland Sweden United Kingdom

References

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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.

Reference Type DERIVED
PMID: 34753762 (View on PubMed)

Related Links

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Other Identifiers

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GPPAD-04

Identifier Type: -

Identifier Source: org_study_id