PeRsOnalising Treatment Of Diabetic Nephropathy:

Diabetes Mellitus, Type 1 Clinical Trial

— PROTON  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03509454
• Other study ID #: 36000
• Status: Completed
• First received: April 10, 2018
• Last updated: April 16, 2018
• Start date: April 1, 2016
• Est. completion date: April 1, 2018

Study information

• Verified date: April 2018
• Source: Steno Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: April 1, 2018
• Est. primary completion date: October 1, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Complications
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetic Nephropathies
• Kidney Diseases

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center	Gentofte	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Peter Rossing

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The microvascular function by estimating the glycocalyx thickness	Glycocalyx thickness assessed as perfused boundary region by a hand-hold camera (GlycoCheck)	2019
Secondary	Gut microbiome	Characterisation of the gut microbiota and markers of gastrointestinal inflammation	2019
Secondary	Urine and plasma Flow Cytometry Analysis (FACS)	cell types related to inflammation	2019
Secondary	Metabolomics in plasma	metabolite risk score in plasma	2019
Secondary	Metabolomics in urine	metabolite risk score in urine	2019
Secondary	proteomics in urine	proteomic risk score in urine	2019
Secondary	proteomics in plasma	proteomic risk score in plasma	2019
Secondary	Autonomic neuropathy	beat to beat variation (R-R test) upon Deep breathing	2019
Secondary	peripheral neuropathy	vibration perception threshold	2019