Assessing the Role of the Gut Microbiome and of the Intestinal Barrier Integrity in the Immune Pathogenesis of Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Preservation of the residual insulin-producing beta cell mass
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
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.
入排标准
- 年龄范围
- 7 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Preservation of the residual insulin-producing beta cell mass
时间窗: 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
时间窗: 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.
次要结局
- 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)
研究者
Marika Falcone
Group Leader
IRCCS San Raffaele