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NCT Number: NCT05767450

Intervention on New Onset-T1D Children

A pilot proof of concept clinical trial will be performed to demonstrate the restoration of gut barrier integrity by administration of beneficial anti-inflammatory gut microbial strains (Lactobacilli-enriched Vivomixx® probiotic) to new onset Type 1 Diabetes Children.

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Key information

Conditions

Type 1 Diabetes Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

7 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

This is an interventional randomized, 2-arm, single-blind, single-center, placebo-controlled mechanistic clinical trial (1:1).

One sachet of probiotic for children < 10 years old or two sachets for subjects > 10 years old dissolved into water or noncarbonated drinks will be administered every day for 90 consecutive days.The primary end point of the study will be the preservation of the residual insulin-producing beta-cell mass measured as the change in C-peptide values at 12 months after the beginning of treatment. Moreover, the investigators will collect blood samples for serological analysis (autoantibodies detection, measurement of biomarkers of gut barrier integrity) and immunological profiling; fecal samples for microbiome and metabolomic analysis. Finally the investigators will assess whether the response to Vivomixx® probiotic remains stable over a long-term period, that is in the absence of active treatment.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Clinical diagnosis of insulin-dependent type 1 diabetes
  • Positive for at least one islet autoantibody (ICA, GADA, IA-2, IAA, ZnT8)
  • No more than 3 months from first insulin injection
  • ≥ 7 to < 18 year old

Exclusion criteria

  • Diagnosed with celiac disease, IBD or other intestinal inflammatory pathologies
  • Diagnosed with tuberculosis, hepatitis B or C, HIV, or active EBV or CMV infection; significant cardiac disease; conditions associated with immune dysfunction or hematologic dyscrasia (including malignancy, lymphopenia, thrombocytopenia, or anemia); liver or renal dysfunction.
  • Ongoing use of systemic medications other than insulin.
  • Recent administration of antibiotics (1 months prior to treatment)
  • Deemed unlikely or unable to comply with the protocol or have any complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk.

Treatment and study plan

Probiotic Vivomixx®

Dietary Supplement

The correct number of Vivomixx® sachets are given to parents with the indication to administer the dietary supplement as dissolved in drinking water or non-carbonated drinks.

Other names: VSL#3, Visbiome®

Placebo

Dietary Supplement

The correct number of Placebo sachets are given to parents with the indication to administer the dietary supplement as dissolved in drinking water or non-carbonated drinks.

Primary outcomes

  1. Preservation of the residual insulin-producing beta cell mass

    Time frame: through study completion, an average of 1 year

    The primary outcome of the study will be the preservation of the residual insulin-producing beta-cell mass in newly diagnosed T1D patients that received the probiotic Vivomixx® in comparison to those receiving placebo. This parameter will be reported as the change in C-peptide values (ng/mL) before starting treatment (baseline) and 12 months after treatment initiation.

  2. Glycemic control by Time-in-Range (TIR) monitoring

    Time frame: through study completion, an average of 1 year

    Glycemic control will be monitored in newly diagnosed T1D patients that received the probiotic Vivomixx® in comparison to those receiving placebo. This parameter will be reported as the change in TIR values (%) - that is the percentage of time in which blood glucose (blood sugar) remains in the safe target range of 70-180mg/dL - recorded before starting treatment (baseline) and 12 months after treatment initiation.

Secondary outcomes

  1. Gut barrier integrity

    Time frame: through study completion, an average of 1 year

    The levels of zonulin and LBP will be measured in the serum before starting Vivomixx® or placebo administration (baseline), 3 months and 6 months after treatment initiation, as biomarkers used to determine the integrity of the intestinal epithelium in humans.

  2. Gut microbiome profile

    Time frame: through study completion, an average of 1 year

    The gut microbiota composition will be analyzed on fecal samples collected before starting Vivomixx or placebo administration (baseline), 3 months and 6 months after treatment, 16S ribosomal RNA (rRNA) sequencing.

  3. Measurement by flow cytometry of differences in the percentages of regulatory and inflammatory CD4 T cells

    Time frame: through study completion, an average of 1 year

    Changes in circulating regulatory and inflammatory CD4 T cell subsets (Treg, Th1, Th2, Th17) will be evaluated by flow cytometry of the expression of:

    • CD4, FOXP3 (Treg)
    • CD4, CRTH2 (Th2)
    • CD4, Tbet (Th1)
    • CD4, RORgt (Th17)

    Results will be expressed in term of percentage (%) of CD4 T cells expressing the molecules

  4. Measurement by flow cytometry of differences in the percentages of MAIT cells and TCR gamma Delta T cells

    Time frame: through study completion, an average of 1 year

    Changes in circulating MAIT and TCR gammaDelta T cell subsets will be evaluated by flow cytometry of the expression of CD3, TCRgD, CD161, TCRva7.2

    Results will be expressed in term of percentage (%) of cells expressing CD3, TCRgD molecules (that are TCRgammaDelta T cells) and CD3, CD161, TCRva7.2 molecules (that are MAIT cells)

  5. Measurement by flow cytometry of differences in the percentages of innate lymphoid cells

    Time frame: through study completion, an average of 1 year

    Changes in circulating MAIT and TCR gammaDelta T cell subsets will be evaluated by flow cytometry of the expression of Lineage markers, c-kit, CRTH2

    Results will be expressed in term of percentage (%) of Lineage-negative cells expressing c-kit or CRTH2 molecules.

Study contacts

Contact information is provided by the study sponsor or research team.

Marika Falcone, MD

CONTACT

[email protected]

00390226434890

Sponsors and collaborators

Lead sponsor

IRCCS San Raffaele

Other

Registry information

Official study title

Assessing the Role of the Gut Microbiome and of the Intestinal Barrier Integrity in the Immune Pathogenesis of Type 1 Diabetes

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Mar 14, 2023
Registry last updated
Dec 2, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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