Clinical Trial Technology Development for the Validation of Surrogate Prognostic Markers in Patients With Diabetic Nephropathy
Worldwide, the most common cause of chronic kidney disease (CKD) and end stage renal disease (ESRD) is diabetes. Unlike the past, in south korea, diabetes account for more than 40% of ESRD. According to WHO reports in 1998, 100 million people had type 2 diabetes in 1997, and there is expected to increase by 300 million people in 2025. In addition, the expected survival time of patients with diabetes increase compared to previous. In the future, ESRD due to type 2 diabetes is expected to have a significant impact on the health industry. Therefore, prevention of progression to CKD and ESRD in diabetic patients is important to aspect of national health and economic problems. How to stop the progression of diabetic nephropathy is part of modern medicine to be solved.
Strict glycemic control, blood pressure regulation, and use of renin-angiotensin system (RAS) blockers inhibit the development and progression of diabetic nephropathy. Microalbuminuria in diabetic patients has been recognized as a predictor of progression of diabetic nephropathy. Thus, the prevention of elevated urinary albumin excretion is an important therapeutic target for the prevention of renal and cardiovascular events.
In patients with diabetes and hypertension, the drugs that block the RAS are used to treat proteinuria, but still a large number of patients with proteinuria are uncontrolled. In addition, ACE inhibitors or ARB agents actually have a limited effect on reducing the risk of cardiovascular or renal outcome. Also, sulodexide or pentoxyphylline which is reducing proteinuria have some weak evidence in terms of efficacy and safety. Therefore, the introduction of new alternative drugs are required.
Already several study reported that calcitriol or paricalcitol in the renal injury model have renopreventive effect. In addition, in diabetic renal injury mice model reported that vitamin D receptor deficiency leads to glomerulosclerosis. Inhibition of the RAS with combination of paricalcitol and RAS inhibitors effectively prevent renal injury in diabetic nephropathy. Recently, Dick de Zeeuw et al reported that addition of paricalcitol to RAS inhibition safely lower residual albuminuria in patients with diabetic nephropathy. Recent studies reported that elevated concentrations of serum markers of the TNFα and Fas-pathways are strongly associated with decreased renal function in diabetic patients. However, the role of these markers in early progressive renal function decline are not clear. Therefore, the objective of this study is to identify the renoprotective effect as an new treatment of activated vitamin D (Calcitriol) indicating the TNF-α-related anti-inflammatory action and to seek the role as an important biomarker that the changes of TNFR in diabetic nephropathy can predict response to treatment.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Anticipé)
Phase
- Phase 4
Contacts et emplacements
Lieux d'étude
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-
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Seoul, Corée, République de, 110-744
- Recrutement
- Seoul National University Hospital
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Contact:
- Yonsu Kim, M.D., Ph.D
- Numéro de téléphone: 82-2-2072-2264
- E-mail: yonsukim@snu.ac.kr
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Contact:
- Dongki Kim, M.D., Ph.D
- Numéro de téléphone: 82-2-2072-2303
- E-mail: dkkim73@gmail.com
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Chercheur principal:
- Yonsu Kim, Ph.D.
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Sous-enquêteur:
- Dongki Kim, M.D., Ph.D
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Sous-enquêteur:
- Sumi Lee, M.D.
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Seoul, Corée, République de
- Pas encore de recrutement
- Seoul National University Boramae Medical Center
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Contact:
- Jungpyo Lee, M.D., Ph.D
- Numéro de téléphone: 82-2-870-2261
- E-mail: kjwa1@medimail.co.kr
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Sous-enquêteur:
- Jungpyo Lee, M.D., Ph.D
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- patients age 19-80 years
- Clinically proven diabetic nephropathy
- MDRD eGFR >= 30mL/min/1.73m2
- Patients with residual urine protein/creatinine ratio >= 200mg/g
- Adequate blood pressure control as treated systolic blood pressure <=140 or diastolic <=90 mmHg with RAS inhibitor for more than 3months
- Serum intact PTH <500 mg/dL
- Serum calcium <10.2 mg/dL
- Patients who have not been treated vitamin D within the 3months prior to signing the informed consent form
Exclusion Criteria:
- Patients age <19 years or > 80years
- Patients with rapidly progressive glomerulonephritis
- Patients requiring renal replacement therapy immediately
- Hypercalcemia(Uncorrected serum calcium level >10.2 mg/dL) within recent 3month
- Malignant hypertension
- Heart failure (New York Heart Association functional class II to IV or LVEF <40%)
- Severe chronic obstructive lung disease
- Decompensated liver disease (ALT >3X upper normal limit)
- Known allergy or hypersensitivity to vitamin D
- Current treatment with steroids and/or immunosuppressive agents
- Active primary malignancy requiring treatment or survival limits less than 2years
- History of noncompliance to medical regimen
- Inability to give an informed consent or to cooperate with researchers
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Dépistage
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Comparateur placebo: Placebo
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Expérimental: Calcitriol
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dosage of 0.5mcg administered orally once daily for 12 month
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Changes in renal function with proteinuria
Délai: 12 month after administration
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Comparison of in GFR level from baseline Comparison of proteinuria amount checked by random urine protein/creatinine ratio
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12 month after administration
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
changes in sTNFR and TNF-related proteins
Délai: 12 months after administration
|
Comparison of serum TNFR1, TNFR2 levels from baseline
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12 months after administration
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chaise d'étude: Yonsu Kim, M.D., Ph.D, Seoul National University Hospital
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Anticipé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
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
- Maladies urologiques
- Maladies du système endocrinien
- Complications du diabète
- Diabète sucré
- Maladies rénales
- Néphropathies diabétiques
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Micronutriments
- Modulateurs de transport membranaire
- Vitamines
- Agents de conservation de la densité osseuse
- Hormones et agents régulateurs du calcium
- Agents vasoconstricteurs
- Agonistes des canaux calciques
- Calcitriol
Autres numéros d'identification d'étude
- SNUH-TNFR
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