PeRsOnalising Treatment Of Diabetic Nephropathy: (PROTON)
PeRsOnalising Treatment Of Diabetic Nephropathy: From Albuminuria to Multidimensional Characterisation of Diabetic Nephropathy - a Cross-sectional Study
Background: Today diabetic nephropathy is a frequent, and the most lethal and costly complication of diabetes. Although treating blood pressure with agents blocking renin angiotensin system has improved outcome, the prognosis is still poor and no new interventions have been successful during the past decade. There is an urgent need for discovery of new pathways behind the development and progression of diabetic nephropathy as well as of biomarkers which can identify subjects at risk of developing adverse events. Objective: By using a multidimensional 'omics' approach, we aim to search for novel proteins, metabolites and pathways that will point to the putative new mechanisms which underlie the early renal decline.
Design: Cross-sectional study, with long-term register-based follow-up. Study population: 160 patients with type 1 diabetes recruited from Steno Diabetes Center Copenhagen stratified based on stage of diabetic kidney disease, and 50 healthy non-diabetic controls. Endpoints: Primary endpoint: Glycocalyx thickness, assessed as perfused boundary region. Secondary endpoints: Gut microbiome characterisation and markers of gastrointestinal inflammation, autonomic and periphery neuropathy, urine and plasma Flow Cytometry Analysis (FACS), metabolomics and proteomics in plasma and urine, and other potential biomarkers.
研究概览
详细说明
研究类型
注册 (实际的)
联系人和位置
学习地点
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Copenhagen
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Gentofte、Copenhagen、丹麦、2820
- Steno Diabetes center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
- Patients with type 1 diabetes
- Written informed consent must be provided before participation
- Male or female patients >18 years of age with a diagnosis of type 1 diabetes (WHO criteria)
- Persistent urinary albumin creatinine ratio (UACR) assessed from EPJ (Electronic Patient Journal):
- < 30 mg/g in 2 out of 3 consecutive samples (normoalbuminuria)
- 30 - 299 mg/g in 2 out of 3 consecutive samples (microalbuminuria)
≥ 300 mg/g in 2 out of 3 consecutive samples (macroalbuminuria) - at least 30 with concurrent eGFR < 60 ml/min/1.73m2
2. Control subjects without diabetes
- Written informed consent must be provided before participation.
- Male or female patients >18 years of age without a diagnosis of diabetes (assessed by Hb1Ac, haemoglobin and creatinine)
Exclusion Criteria: (Both subjects with and without diabetes)
- Non-diabetic kidney disease as indicated by medical history and/or laboratory findings
- Renal failure (eGFR<15 ml/min/1.73m2), dialysis or kidney transplantation
- Change in RAAS blocking treatment during the last month
- Treatment with antibiotics during the last 2 month
- Pregnancy or breastfeeding (urine HCG is performed on all fertile women)
- Patients who, in the judgement of the investigator, is incapable to participate
- For controls: Other diseases or intake of medicine which in the judgement of the investigator could affect the results, specifically renal, cardiovascular or inflammatory/infectious diseases should be considered for exclusion
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
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Type 1 DM, Normo albuminuric
Type 1 diabetics with no history of albumnuria (UACR < 30 mg/g in 2 out of 3 consecutive samples)
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Type 1 DM, Micro albuminuric
Type 1 diabetics with history of micro albumnuria (UACR 30-299 mg/g in 2 out of 3 consecutive samples)
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Type 1 DM, Macro albuminuric
Type 1 diabetics with history of macro albumnuria (UACR 30-299 mg/g in 2 out of 3 consecutive samples)
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Healthy subjects
Subjects with no history of diabetes, other diseases or intake of medicine which in the judgement of the investigator could affect the results, specifically renal, cardiovascular or inflammatory/infectious diseases should be considered for exclusion.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
The microvascular function by estimating the glycocalyx thickness
大体时间:2019
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Glycocalyx thickness assessed as perfused boundary region by a hand-hold camera (GlycoCheck)
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2019
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Gut microbiome
大体时间:2019
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Characterisation of the gut microbiota and markers of gastrointestinal inflammation
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2019
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Urine and plasma Flow Cytometry Analysis (FACS)
大体时间:2019
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cell types related to inflammation
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2019
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Metabolomics in plasma
大体时间:2019
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metabolite risk score in plasma
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2019
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Metabolomics in urine
大体时间:2019
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metabolite risk score in urine
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2019
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proteomics in urine
大体时间:2019
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proteomic risk score in urine
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2019
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proteomics in plasma
大体时间:2019
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proteomic risk score in plasma
|
2019
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Autonomic neuropathy
大体时间:2019
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beat to beat variation (R-R test) upon Deep breathing
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2019
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peripheral neuropathy
大体时间:2019
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vibration perception threshold
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2019
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合作者和调查者
调查人员
- 学习椅:peter Rossing、Steno Diabetes Center Copenhagen
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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