Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy

Study Overview
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Brief Summary
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Traditionally MCN is treated with a high dose of prednisolone, which induces remission in 60-90% of patients. Prednisolone treatment contains numerous side effects and the current dose is empiric. Given the lack of efficacy evidence and the risk associated with the currently accepted treatment regimen there is a need to characterize the outcome in MCN further, and to establish new, and potentially less toxic treatment regimens. The aim is to examine if treatment with reduced dose of prednisolone in combination with activated vitamin D is as effective as standard high dose prednisolone in achieving remission and preventing relapse in MCN, and if reduced dose prednisolone is associated with fewer side effects compared to standard dose. Furthermore, the study will examine the influence of prednisolone metabolism on the efficacy and side effects of prednisolone in the treatment of MCN.

Official Title
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Treatment of Primary Minimal Change Nephropathy: A Randomized Open-labeled Non-inferiority Study on Prednisolone and Vitamin D

Conditions
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Minimal Change Disease, Nephrotic Syndrome

Intervention / Treatment
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* Drug: Prednisolone
* Drug: Alfacalcidol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven minimal change nephropathy If earlier minimal change: No relapse in 5 years, and earlier only treated with prednisolone Nephrotic syndrome Age more than 18 years Exclusion Criteria: Cancer except from basal cells carcinoma Lymphoproliferative disease Pregnancy eGFR < 30 ml/min/1,73m2 (CKD-EPI) Allergy No danish language No ability to give informed prove

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High dose prednisolone<br>Prednisolone 1 mg/kg/day | Drug: Prednisolone<br>* Tablet prednisolone<br>* Other names: Prednisone;|
| Experimental: Alfacalcidol and low dose prednisolone<br>Alfacalcidol 0,5 microgram/day and Prednisolone 0,5 mg/kg/day | Drug: Prednisolone<br>* Tablet prednisolone<br>* Other names: Prednisone;Drug: Alfacalcidol<br>* Capsule alfacalcidol 0,5 microgram/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission | Time from treatment to remission and the frequency of patients reaching remission on treatment | 4 to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse | Frequency of relapse | 4 weeks to 1 year after remission | 
| Side effects to treatment | The side effects to prednisolone are assessed using questionnaires by both patients and doctors, including SF36 and Cushing QoL. The Glucocorticoid Toxicity Index will be used to quantitate prednisolone-related morbidity. | 4 weeks to 1 year after remission | 
| Concentration of Prednisolone in saliva | Measurement of prednisolone metabolism by saliva test and genetic analysis of specific liver enzymes | 4 weeks after initiating prednisolone treatment | 
| Rates of genetic polymorphism, including HLA variations | Genomic HLA typing (HLA-class I: A, B and C and HLA-class II: DM, DO, DP, DQ and DR) will be performed to examine if specific HLA-alleles are more frequent in patients with MCN. Potential modifying genes that theoretically have pathophysiological impact on MCN will be sequenced using targeted next generation sequencing. | Blood test at baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prednisolone, alfacalcidol, Minimal change nephropathy