Type 1 Diabetes
Conditions
Keywords
Gut microbiome, Intestinal barrier integrity
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.
Interventions
DIETARY_SUPPLEMENTProbiotic Vivomixx®
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.
DIETARY_SUPPLEMENTPlacebo
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.
Sponsors
IRCCS San Raffaele
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
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.
Intervention model description
Interventional, randomized (1:1), 2-arm, single-center, placebo controlled
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Preservation of the residual insulin-producing beta cell mass | 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. |
| Glycemic control by Time-in-Range (TIR) monitoring | 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
| Measure | Time frame | Description |
|---|---|---|
| Measurement by flow cytometry of differences in the percentages of regulatory and inflammatory CD4 T cells | 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 |
| Gut barrier integrity | 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. |
| Measurement by flow cytometry of differences in the percentages of innate lymphoid cells | 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. |
| 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 | 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) |
| Gut microbiome profile | 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. |
Countries
Italy
Contacts
Primary ContactMarika Falcone, MD
Outcome results
None listed