Effect of Prebiotic Fibre on Glycemic Control, Gut Microbiota, and Intestinal Permeability in Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 144
- 试验地点
- 6
- 主要终点
- Change in frequency of hypoglycemia
研究概览
简要总结
Evidence suggests that prebiotic fibre can correct dysbiosis, reduce intestinal permeability and improve glycemic control. The investigators hypothesize that microbial changes induced by prebiotics contribute to gut and endocrine adaptations that reduce glucose fluctuations, including less hyper- and hypoglycemia in type 1 diabetes (T1D). The primary objective is to compare the change in frequency of hypoglycemia from baseline to 6 months in n=144 individuals with T1D treated with a 6-month course of prebiotic or placebo as an adjunct to insulin. Secondary objectives will be aimed at understanding the mechanisms by which the prebiotics could affect glycemic control.
详细描述
The investigators hypothesize that, as an adjunct to insulin, prebiotic supplementation will reduce the frequency of hypoglycemia and improve glycemic variability that is accompanied by enhanced serum C-peptide levels, a reduction in intestinal permeability and systemic inflammation, and altered gut microbiota.
Primary Objective To compare the change in frequency of hypoglycemia from baseline to 6 months in individuals with T1D treated with a 6-month course of prebiotic or placebo as an adjunct to insulin.
Secondary Objectives
- To determine the change in glycemic variability and glycemic control using Continuous Glucose Monitor (CGM) metrics including: percentage change in Time In-, Below-, and Above-Range (i.e. TIR, TBR, and TAR) and A1C from baseline to 6 months in those treated with prebiotic or placebo.
- To compare the change in stimulated C-peptide and pro-insulin from baseline to 6 months.
- To determine the change in IP from baseline to 6 months.
- To determine the change in serum inflammatory markers (IL-6, IFN-gamma, TNF, C-reactive protein, and IL-10).
- To examine quality of life (QOL) and fear of hypoglycemia ratings, and adverse reactions (severe hypoglycemia, diabetic ketoacidosis, side effects).
- To examine prebiotic-induced changes in gut microbiota composition and function (shotgun sequencing) and their metabolic by-products (fecal and serum metabolomics).
- To compare the change in frequency of hypoglycemia from baseline to 9 months to determine persistence of effects post-intervention.
- To determine the change in glycemic variability from baseline to 9 months to determine persistence of effects post-intervention.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The prebiotic and placebo are both white powders with similar sweet taste and dissolve in water.
入排标准
- 年龄范围
- 7 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with type 1 diabetes (based on Diabetes Canada 2018 Clinical Practice Guideline diagnostic criteria) in the previous 12 months.
- •Age 7 years and above (as per our pilot trial and able to complete the required tests).
- •Diagnosed with type 1 diabetes (based on Diabetes Canada 2018 Clinical Practice Guideline diagnostic criteria) in the previous 12 months.
- •Age 7 to 17 years of age.
排除标准
- •Regular use of medications or supplements that could affect gut microbiota (examples: antibiotics, probiotic or prebiotic supplements, laxatives) within 3 months prior to enrollment.
- •Previous intestinal surgery.
- •Another chronic medical condition that could affect gut microbiota or intestinal permeability (examples: Crohn's disease, Celiac disease, colitis, irritable bowel syndrome)
- •Presence of active infection, pregnancy or lactation.
研究组 & 干预措施
Prebiotic
Oligofructose-enriched inulin
干预措施: Prebiotic (Dietary Supplement)
Placebo
Maltodextrin
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Change in frequency of hypoglycemia
时间窗: 6 months
Blood glucose \<3.9 mmol/L from continuous glucose monitor data
次要结局
- Change in glycemic control(6 months)
- Change in stimulated C-peptide(6 months)
- Change in Intestinal permeability(6 months)
- Change in lipopolysaccharide(6 months)
- Change in Inflammatory marker IL-6(6 months)
- Change in Inflammatory marker IFN-γ(6 months)
- Change in Inflammatory marker TNF(6 months)
- Change in Inflammatory marker CRP(6 months)
- Change in Inflammatory marker IL-10(6 months)
- Change in quality of life(6 months)
- Change in fear of hypoglycemia(6 months)
- Change in gut microbiota composition(6 months)
- Change in serum metabolite concentration(6 months)
- Change in fecal metabolite concentrations(6 months)
- Change in frequency of hypoglycemia post-intervention(9 months)
- Change in glycemic control post-intervention(9 months)
- Change in glycemic variability(6 months)
- Change in serum proinsulin(6 months)
- Change in gut microbiota function(6 months)
- Change in glycemic variability post-intervention(9 months)
研究者
Dr. Raylene Reimer
Professor
University of Calgary