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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Nephrotic Syndrome; Minimal Change Disease
• Intervention / Treatment: Drug: Prednisolone; Drug: Alfacalcidol

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tilde Kristensen, MD; Phone Number: +45 78447039; Email: tilde.kristensen@rm.dk
• Study Contact Backup: Name: Per Ivarsen; Phone Number: +45 40460063; Email: perivars@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital
  • Viborg, Denmark
    • Regional Hospital Viborg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Study Chair: Per Ivarsen, Aarhus University Hospital

Publications and helpful links

General Publications

• Azukaitis K, Palmer SC, Strippoli GF, Hodson EM. Interventions for minimal change disease in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2022 Mar 1;3(3):CD001537. doi: 10.1002/14651858.CD001537.pub5.
• Kristensen T, Birn H, Ivarsen P. A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN). Trials. 2021 Jul 12;22(1):442. doi: 10.1186/s13063-021-05393-4.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): February 14, 2024
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: July 3, 2017
• First Submitted That Met QC Criteria: July 4, 2017
• First Posted (Actual): July 7, 2017

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Prednisolone; alfacalcidol; Minimal change nephropathy
• Additional Relevant MeSH Terms: Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Nephrotic Syndrome; Nephrosis; Nephrosis, Lipoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Micronutrients; Vitamins; Bone Density Conservation Agents; Prednisolone; Prednisone; Alfacalcidol; Hydroxycholecalciferols
• Other Study ID Numbers: ADAPT in MCN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No