Clinical trial NCT03509454: PeRsOnalising Treatment Of Diabetic Nephropathy:
Official title: PeRsOnalising Treatment Of Diabetic Nephropathy: From Albuminuria to Multidimensional Characterisation of Diabetic Nephropathy - a Cross-sectional Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus, Type 1
Diabetes Complications
Diabetic Nephropathies
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
First posted: 2018-04-26
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 160 patients with type 1 diabetes and different stages of diabetic nephropathy (50 with normoalbuminuria; 50 with microalbuminuria; and 60 with macroalbuminuria -including at least 30 with concurrent estimated Glomerular Filtration Rate (eGFR) \< 60 ml/min/1.73m2) compared to 50 healthy non-diabetic controls.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The microvascular function by estimating the glycocalyx thickness
timeFrame: 2019
Secondary outcomes:
measure: Gut microbiome
timeFrame: 2019
measure: Urine and plasma Flow Cytometry Analysis (FACS)
timeFrame: 2019
measure: Metabolomics in plasma
timeFrame: 2019
measure: Metabolomics in urine
timeFrame: 2019
measure: proteomics in urine
timeFrame: 2019
measure: proteomics in plasma
timeFrame: 2019
measure: Autonomic neuropathy
timeFrame: 2019
measure: peripheral neuropathy
timeFrame: 2019
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center
state: Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: peter Rossing
role: STUDY_CHAIR
References: