PeRsOnalising Treatment Of Diabetic Nephropathy: (PROTON)

Peter Rossing

Status: Completed

Conditions: Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetes Complications

Study type: Observational

Funder types: Other

Identifiers

NCT03509454

36000

Details and patient eligibility

About

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.

Full 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.

Enrollment: 210 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

210 participants in 4 patient groups

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)

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)

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)

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.