A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)

Abstract Background Minimal change nephropathy (MCN) is a common cause of nephrotic syndrome in both adults and children. International guidelines recommend treatment with prednisolone 1 mg/kg/day to adults. This dose is derived from an empirically established dose in children, although children gen...

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Main Authors: Tilde Kristensen, Henrik Birn, Per Ivarsen
Format: Article
Language:English
Published: BMC 2021-07-01
Series:Trials
Subjects:
Online Access:https://doi.org/10.1186/s13063-021-05393-4
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spelling doaj-acf3b7af2f71405cb9edca336c19f5372021-07-18T11:38:14ZengBMCTrials1745-62152021-07-0122111010.1186/s13063-021-05393-4A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)Tilde Kristensen0Henrik Birn1Per Ivarsen2Department of Internal Medicine, renal unit, Regional Hospital Viborg, and Department of Clinical Medicine, Aarhus UniversityDepartment of Nephrology, Aarhus University Hospital and Department of Biomedicine, Aarhus UniversityDepartment of Nephrology, Aarhus University Hospital, and Department of Clinical Medicine, Aarhus UniversityAbstract Background Minimal change nephropathy (MCN) is a common cause of nephrotic syndrome in both adults and children. International guidelines recommend treatment with prednisolone 1 mg/kg/day to adults. This dose is derived from an empirically established dose in children, although children generally attain remission faster and relapse more rapidly than adults. Prednisolone is associated with multiple and serious adverse events. Activated vitamin D has been shown to reduce albuminuria in other glomerular renal diseases with a minimum of adverse events. This study tests the hypothesis that a new treatment regimen in MCN combining reduced dose prednisolone and active vitamin D is as efficient in inducing remission and has fewer and less severe adverse events than standard prednisolone. Furthermore, we aim to establish models allowing for more personalized medicine based on assessment of the individual’s prednisolone metabolism. Methods A randomised controlled multicentre non-inferior unblinded trial including 96 adult, incident patients with biopsy-proven MCN, albuminuria > 3 g/day, and an estimated glomerular filtration rate (eGFR) > 30 ml/min from renal departments in Denmark. Patients are randomised to standard prednisolone (1 mg/kg/day) or reduced prednisolone (0.5 mg/kg/day) and alfacalcidol (0.5 μg/day). The primary outcome is the rate of remissions after 16 weeks and the time from diagnosis to remission. The study will include a saliva test to characterise prednisolone pharmacokinetics and compare them to genetic variations in specific liver enzymes responsible for prednisolone metabolism. Discussion Reducing the prednisolone dose is expected to reduce the number of severe adverse events. This study will examine if reduced prednisolone dose with active vitamin D but without additional immunosuppression is feasible in the treatment of MCN and will reduce the number of adverse events. The findings can potentially change current guidelines for treatment of MCN in adults. Additional outcomes on inter-individual pharmacokinetic and metabolic variations may allow for a more personalised treatment strategy. Trial registration EudraCT 2017-001206-16, ClinicalTrials.gov NCT03210688 . Registered on June 3, 2017.https://doi.org/10.1186/s13063-021-05393-4Minimal change nephropathyPrednisoloneActivated vitamin DNephrotic syndromeAdverse eventsPharmacokinetics
collection DOAJ
language English
format Article
sources DOAJ
author Tilde Kristensen
Henrik Birn
Per Ivarsen
spellingShingle Tilde Kristensen
Henrik Birn
Per Ivarsen
A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)
Trials
Minimal change nephropathy
Prednisolone
Activated vitamin D
Nephrotic syndrome
Adverse events
Pharmacokinetics
author_facet Tilde Kristensen
Henrik Birn
Per Ivarsen
author_sort Tilde Kristensen
title A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)
title_short A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)
title_full A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)
title_fullStr A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)
title_full_unstemmed A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)
title_sort randomised controlled unblinded multicentre non-inferiority trial with activated vitamin d and prednisolone treatment in patients with minimal change nephropathy (adaptinmcn)
publisher BMC
series Trials
issn 1745-6215
publishDate 2021-07-01
description Abstract Background Minimal change nephropathy (MCN) is a common cause of nephrotic syndrome in both adults and children. International guidelines recommend treatment with prednisolone 1 mg/kg/day to adults. This dose is derived from an empirically established dose in children, although children generally attain remission faster and relapse more rapidly than adults. Prednisolone is associated with multiple and serious adverse events. Activated vitamin D has been shown to reduce albuminuria in other glomerular renal diseases with a minimum of adverse events. This study tests the hypothesis that a new treatment regimen in MCN combining reduced dose prednisolone and active vitamin D is as efficient in inducing remission and has fewer and less severe adverse events than standard prednisolone. Furthermore, we aim to establish models allowing for more personalized medicine based on assessment of the individual’s prednisolone metabolism. Methods A randomised controlled multicentre non-inferior unblinded trial including 96 adult, incident patients with biopsy-proven MCN, albuminuria > 3 g/day, and an estimated glomerular filtration rate (eGFR) > 30 ml/min from renal departments in Denmark. Patients are randomised to standard prednisolone (1 mg/kg/day) or reduced prednisolone (0.5 mg/kg/day) and alfacalcidol (0.5 μg/day). The primary outcome is the rate of remissions after 16 weeks and the time from diagnosis to remission. The study will include a saliva test to characterise prednisolone pharmacokinetics and compare them to genetic variations in specific liver enzymes responsible for prednisolone metabolism. Discussion Reducing the prednisolone dose is expected to reduce the number of severe adverse events. This study will examine if reduced prednisolone dose with active vitamin D but without additional immunosuppression is feasible in the treatment of MCN and will reduce the number of adverse events. The findings can potentially change current guidelines for treatment of MCN in adults. Additional outcomes on inter-individual pharmacokinetic and metabolic variations may allow for a more personalised treatment strategy. Trial registration EudraCT 2017-001206-16, ClinicalTrials.gov NCT03210688 . Registered on June 3, 2017.
topic Minimal change nephropathy
Prednisolone
Activated vitamin D
Nephrotic syndrome
Adverse events
Pharmacokinetics
url https://doi.org/10.1186/s13063-021-05393-4
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