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

NCT04769037 | Active Not Recruiting DMC

• 1 other identifier: GPPAD-04
• Study Type: interventional
• Target: 1,149
• Locations: 5 countries
• Sites: 8

Brief 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 cumulative incidence of beta-cell autoantibodies in childhood.

Conditions

Diabetes Mellitus, Type 1

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Through study completion, up to 6.5 years

Secondary Outcomes (5)

• Persistent confirmed beta-cell autoantibodies

  Through study completion, up to 6.5 years

• Diabetes

  Through study completion, up to 6.5 years

• Transglutaminase antibodies

  Through study completion, up to 6.5 years

• Respiratory infection rate

  1 year

• Measurement of Safety parameters

  from Baseline until 30 days after end of supplementation

Other Outcomes (5)

• Allergy

  Through study completion, up to 6.5 years

• Antibody response (IgG titres) to vaccines

  at age 6 months (rotavirus) and at age 2 years (MMR)

• Alterations of the gut microbiome or blood metabolome

  from baseline to age 12 months

Study Arms (2)

B. infantis

ACTIVE COMPARATOR

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

Dietary Supplement: B. infantis

Placebo

PLACEBO COMPARATOR

Lactose identical in appearance and taste to the active supplement

Dietary Supplement: Placebo

Interventions

B. infantis DIETARY_SUPPLEMENT

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

B. infantis

Placebo DIETARY_SUPPLEMENT

Lactose identical in appearance and taste to the active supplement

Placebo

Eligibility Criteria

• Age: 7 Days - 6 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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).-

You may not qualify if:

• 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

Sponsors & Collaborators

• Helmholtz Zentrum München: lead
• Technical University of Munich: collaborator
• Kinderkrankenhaus auf der Bult: collaborator
• University Hospital Carl Gustav Carus: collaborator
• Skane University Hospital: collaborator
• Universitaire Ziekenhuizen KU Leuven: collaborator
• Medical University of Warsaw: collaborator
• Cambridge Biomedical Campus, Cambridge, UK: collaborator
• Royal Victoria Infirmary, Newcastle upon Tyne, UK: collaborator

Study Sites (8)

University Hospitals Leuven Faculty of Medicine, Catholic University of Leuven

Leuven, Belgium

Location

Universitätsklinikum Carl Gustav Carus Technische Universität Dresden

Dresden, Germany

Location

AUF DER BULT, Kinder- und Jugendkrankenhaus

Hanover, Germany

Location

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

Munich, Germany

Location

Department of Paediatrics Medical University of Warsaw

Warsaw, Poland

Location

Lund University, Skane University Hospital SUS

Malmo, Sweden

Location

University Department of Paediatrics, Cambridge Biomedical Campus

Cambridge, United Kingdom

Location

Royal Victoria Infirmary, Newcastle upon Tyne

Newcastle, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34753762 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Respiratory Tract Infections; Hypersensitivity

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Infections; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director - Institute of Diabetes Research

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: February 24, 2021
• Study Start: April 22, 2021
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 13, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); BE (1); SE (1); DE (3); GB (2)