PeRsOnalising Treatment Of Diabetic Nephropathy:

PeRsOnalising Treatment Of Diabetic Nephropathy: From Albuminuria to Multidimensional Characterisation of Diabetic Nephropathy - a Cross-sectional Study

Sponsors

Lead Sponsor: Peter Rossing

Source Steno Diabetes Center Copenhagen
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.

Overall Status Completed
Start Date April 1, 2016
Completion Date April 1, 2018
Primary Completion Date October 1, 2017
Study Type Observational
Primary Outcome
Measure Time Frame
The microvascular function by estimating the glycocalyx thickness 2019
Secondary Outcome
Measure Time Frame
Gut microbiome 2019
Urine and plasma Flow Cytometry Analysis (FACS) 2019
Metabolomics in plasma 2019
Metabolomics in urine 2019
proteomics in urine 2019
proteomics in plasma 2019
Autonomic neuropathy 2019
peripheral neuropathy 2019
Enrollment 210
Condition
Eligibility

Sampling Method: Non-Probability Sample

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
peter Rossing Study Chair Steno Diabetes Center Copenhagen
Location
Facility: Steno Diabetes Center
Location Countries

Denmark

Verification Date

April 2018

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Steno Diabetes Center Copenhagen

Investigator Full Name: Peter Rossing

Investigator Title: Professor, MD, DMsc

Has Expanded Access No
Condition Browse
Arm Group

Label: Type 1 DM, Normo albuminuric

Description: Type 1 diabetics with no history of albumnuria (UACR < 30 mg/g in 2 out of 3 consecutive samples)

Label: Type 1 DM, Micro albuminuric

Description: Type 1 diabetics with history of micro albumnuria (UACR 30-299 mg/g in 2 out of 3 consecutive samples)

Label: Type 1 DM, Macro albuminuric

Description: Type 1 diabetics with history of macro albumnuria (UACR 30-299 mg/g in 2 out of 3 consecutive samples)

Label: Healthy subjects

Description: 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.

Acronym PROTON
Patient Data No
Study Design Info

Observational Model: Cohort

Time Perspective: Cross-Sectional

Source: ClinicalTrials.gov