Effects of Probiotics and Fibers on Markers of Nephropathy, Inflammation and Endothelial Dysfunction in Persons With Type 1 Diabetes and Albuminuria
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 2
- 主要终点
- Change in albuminuria based on urinary albumin-creatinine ratio (UACR)
研究概览
简要总结
The primary objective is to assess the impact of three months' treatment with pre-/probiotic mix on markers of nephropathy and other comorbidity related to diabetes. A double blinded, randomized, placebo-controlled crossover, single-centre study including 46 patients with type 1 diabetes and albuminuria. The treatment period is 2 x 12 weeks with 6 weeks washout. The primary outcome is to evaluate the effect of pre-/probiotic mix on albuminuria.
详细描述
Recent data has pointed towards a link between gut microbiota and chronic kidney disease (CKD). It is hypothesized that defects in the intestinal barrier due to intestinal dysbiosis, a microbial imbalance in the intestines, allow bacterial toxins and other proinflammatory substances to pass and cause systemic inflammation that damages the endothelium. To reestablish the microbial symbiosis and thereby strengthening the gut barrier different treatments have been investigated. Fibers serve as substrate for the beneficial bacterial strains and probiotics are selected bacteria that exert a beneficial effect on the gut environment. It is hypothesized that a supplement of fructo-oligosaccharides and probiotics (Pre-/probiotic mix) will strengthen the gut barrier and thereby protect the endothelium and kidneys.
The aim of this study is to test whether af Pre-/probiotic mix, will have a beneficial impact on albuminuria in persons with type 1 diabetes and albuminuria.
46 patients with type 1 diabetes and albuminuria will be recruited from Steno Diabetes Center Copenhagen (SDCC) in accordance with the study in- and exclusion criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Allocation will be masked for both participants and investigators. Only after completion of all study visits by all participants and after database lock the randomization code will be opened.
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Persons ≥ 18 years of age with a diagnosis of type 1 diabetes (age at onset <40 years; permanent insulin treatment initiated within 1 year of diagnosis)
- •Albuminuria: UACR > 30 mg/g (in ≥2 out 3 morning spot urine collections prior to randomization)
- •Participants must be on stable renin-angiotensin system blocking treatment 4 weeks before start of study drug and throughout study duration.
- •Able to understand the written participant information and give informed consent
排除标准
- •Non-diabetic kidney disease indicated by medical history and/or laboratory findings
- •Known inflammatory bowel disease (IBD)
- •IBD symptoms due to investigator's opinion
- •Known celiac disease
- •Existing ostomy, malabsorption, history of bowel resection or bariatric surgery.
- •Heart valve replacement or history of endocarditis
- •Known rheumatic disorders treated with anti-inflammatory agents
- •Known hyperthyroidism or hypothyroidism
- •Active immunosuppressant therapy with systemic effect due to investigator's opinion
- •Current cancer treatment or within five years from baseline (except basal cell skin cancer or squamous cell skin cancer)
- •eGFR<15 ml/min/1.73m2, dialysis or kidney transplantation
- •Active antibiotic therapy until 30 days ahead of screening
- •Dietary supplements containing fibers (e.g. psyllium), probiotics or carotenoids until 30 days ahead of screening
- •The receipt of any investigational product 90 days prior to this trial
- •Unable to participate in study procedures
- •Any clinically significant disorder, except for conditions associated with type 1 diabetes, which in the Investigators opinion could interfere with the results of the trial
- •Pregnancy or lactation
- •Participation in another intervention study
结局指标
主要结局
Change in albuminuria based on urinary albumin-creatinine ratio (UACR)
时间窗: 30 weeks. Samples will be collected before and after each og te two treatment periods.
Three morning urine samples will be collected for assessment of UACR. The geometric mean of the 3 samples will be calculated.
次要结局
- Change in 24-hour blood pressure(30 weeks. 24h BP will be performed after each of the two treatment periods.)
- Change in microcirculation evaluated by the GlycoCheck device(30 weeks. GlycoCheck will be performed before and after each of the two treatment periods.)
- Change in systemic inflammation (hs-TNT, TNF-alfa, IL6, IL8, IL1-beta, SAA, sICAM1, sICAM3 and suPAR)(30 weeks. Blood tests will be performed before and after each of the two treatment periods.)
- Change in kidney function (GFR as plasma clearance of 99mTc-DTPA)(30 weeks. 99mTc-DTPA GFR will be performed after each of the two treatment periods.)
- Change in endothelial dysfunction (von Willebrand factor, endothelin-1, ADMA, ICAM-1, VCAM-1 and E-selectin)(30 weeks. Blood tests will be performed before and after each of the two treatment periods.)
- Change in urinary markers of oxidative stress F2-isoprostanes and 8-oxodG(30 weeks. Urine samples will be collected before and after each of the two treatment periods.)
- Change in intestinal inflammation measured by fecal calprotectin(30 weeks. Fecal samples will be collected before and after each of the two treatment periods.)
- Change in biomarkers of intestinal permeability (LPS and zonulin)(30 weeks. Blood tests will be performed before and after each of the two treatment periods.)
- Change in tubular function (NGAL, KIM-1, Beta2microglobulin, hepatocellular growth factor and adiponectin)(30 weeks. Urine samples will be collected before and after each of the two treatment periods.)
- Change in autonomous neuropathy evaluated by VagusTM(30 weeks. Vagus test will be performed before and after each of the two treatment periods.)