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.
Aperçu de l'étude
Statut
Description détaillée
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
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Copenhagen
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Gentofte, Copenhagen, Danemark, 2820
- Steno Diabetes center
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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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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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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The microvascular function by estimating the glycocalyx thickness
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Gut microbiome
Délai: 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)
Délai: 2019
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cell types related to inflammation
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2019
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Metabolomics in plasma
Délai: 2019
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metabolite risk score in plasma
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2019
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Metabolomics in urine
Délai: 2019
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metabolite risk score in urine
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2019
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proteomics in urine
Délai: 2019
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proteomic risk score in urine
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2019
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proteomics in plasma
Délai: 2019
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proteomic risk score in plasma
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2019
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Autonomic neuropathy
Délai: 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
Délai: 2019
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vibration perception threshold
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2019
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chaise d'étude: peter Rossing, Steno Diabetes Center Copenhagen
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 36000
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
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