Assessing the Role of the Gut Microbiome and of the Intestinal Barrier Integrity in the Immune Pathogenesis of Type 1 Diabetes
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Type 1 Diabetes
- Sponsor
- IRCCS San Raffaele
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Preservation of the residual insulin-producing beta cell mass
- Status
- Recruiting
- Last Updated
- last year
Overview
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.
Investigators
Marika Falcone
Group Leader
IRCCS San Raffaele
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.
Outcomes
Primary Outcomes
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.
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
- 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 innate lymphoid 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)