Clinical trial NCT05767450: Intervention on New Onset-T1D Children
Official title: Assessing the Role of the Gut Microbiome and of the Intestinal Barrier Integrity in the Immune Pathogenesis of Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 1 Diabetes
Keywords: Gut microbiome
Intestinal barrier integrity
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2023-03-14
Enrollment: 60
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Interventional, randomized (1:1), 2-arm, single-center, placebo controlled
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Preservation of the residual insulin-producing beta cell mass
timeFrame: through study completion, an average of 1 year
measure: Glycemic control by Time-in-Range (TIR) monitoring
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Gut barrier integrity
timeFrame: through study completion, an average of 1 year
measure: Gut microbiome profile
timeFrame: through study completion, an average of 1 year
measure: Measurement by flow cytometry of differences in the percentages of regulatory and inflammatory CD4 T cells
timeFrame: through study completion, an average of 1 year
measure: Measurement by flow cytometry of differences in the percentages of MAIT cells and TCR gamma Delta T cells
timeFrame: through study completion, an average of 1 year
measure: Measurement by flow cytometry of differences in the percentages of innate lymphoid cells
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: MIlan
country: Italy
facility: Autoimmune Pathogenesis Unit
Study officials:
affiliation: IRCCS San Raffaele
name: Marika Falcone
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.