Intervention on New Onset-T1D Children

NCT05767450 | Recruiting DMC

• 1 other identifier: RF-2019-123-70721
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 1 Diabetes

Keywords

Gut microbiome; Intestinal barrier integrity

Outcome Measures

Primary Outcomes (2)

• Preservation of the residual insulin-producing beta cell mass

  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.

  through study completion, an average of 1 year

• Glycemic control by Time-in-Range (TIR) monitoring

  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.

  through study completion, an average of 1 year

Secondary Outcomes (5)

• Gut barrier integrity

  through study completion, an average of 1 year

• Gut microbiome profile

  through study completion, an average of 1 year

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

  through study completion, an average of 1 year

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

  through study completion, an average of 1 year

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

  through study completion, an average of 1 year

Study Arms (2)

Treated

EXPERIMENTAL

Probiotic name: Vivomixx® Form: powder Dosage: 4,4g/sachet with 450 billion of lactobacilli and bifidobacteria in a base of maltose Frequency: 1 sachet/day for children \<10 year old or 2 sachets/day for children \>10 year old Duration: 90 days

Dietary Supplement: Probiotic Vivomixx®

Untreated

PLACEBO COMPARATOR

Product name: Placebo Form: powder Dosage: 4,4g/sachet containing maltose Frequency: 1 sachet/day for children \<10 year old or 2 sachets/day for children \>10 year old Duration: 90 days

Dietary Supplement: Placebo

Interventions

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.

Also known as: VSL#3, Visbiome®

Treated

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.

Untreated

Eligibility Criteria

• Age: 7 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

Autoimmune Pathogenesis Unit

Milan, Milan, 20132, Italy

RECRUITING

Related Publications (3)

• Dolpady J, Sorini C, Di Pietro C, Cosorich I, Ferrarese R, Saita D, Clementi M, Canducci F, Falcone M. Oral Probiotic VSL#3 Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment. J Diabetes Res. 2016;2016:7569431. doi: 10.1155/2016/7569431. Epub 2015 Dec 8.

  PMID: 26779542 BACKGROUND

• Caballero-Franco C, Keller K, De Simone C, Chadee K. The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G315-22. doi: 10.1152/ajpgi.00265.2006. Epub 2006 Sep 14.

  PMID: 16973917 BACKGROUND

• Korpela R, Niittynen L. Probiotics and irritable bowel syndrome. Microb Ecol Health Dis. 2012 Jun 18;23. doi: 10.3402/mehd.v23i0.18573. eCollection 2012.

  PMID: 23990830 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

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

Study Officials

• Marika Falcone

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marika Falcone, MD

CONTACT

00390226434890; falcone.marika@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be randomized in blind (by a computer) in 1:1 allocations. Participants enrolled in both arms and their parents wil be blinded to treatment as sachets provided will be identical as will be the visual aspect and taste of the Vivomixx probiotic.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Group Leader

Model Details: Interventional, randomized (1:1), 2-arm, single-center, placebo controlled

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: March 14, 2023
• Study Start: December 16, 2022
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)