Tacrolimus Versus Prednisolone for the Treatment of Minimal Change Disease (MinTAC)

Tacrolimus vs Prednisolone for the Treatment Minimal Change Disease

The purpose of this study is to compare the effectiveness of tacrolimus (prograf) versus prednisolone for the treatment of nephrotic syndrome secondary to minimal change disease.

Study Overview

• Status: Completed
• Conditions: Minimal Change Disease
• Intervention / Treatment: Drug: prednisolone; Drug: tacrolimus

Detailed Description

Minimal change disease is a common cause of nephrotic syndrome in adults. Standard treatment is with high dose steroids which is often effective in controlling the nephrotic syndrome but has a high morbidity due to the side effects of the steroids. There is also a high relapse rate,therefore many patients require long term steroid therapy to control their disease which has significant morbidity and mortality. Some patients are or also become steroid resistant. There are studies showing the effectiveness of alkylating agents such as cyclophosphamide but the use of these drugs is limited by their toxicity, including increased rates of infection, cancers and infertility.

Tacrolimus (prograf) is a T-cell specific calcineurin inhibitor that shares similar immunosuppressive actions with cyclosporine A.In other glomerular diseases such as focal segmental glomerulosclerosis and membranous glomerulonephritis, prograf has been shown to be a very effective treatment for proteinuria. This may be due to the immunomodulatory effects on the underlying disease, but there may also be a direct effect of tacrolimus (prograf) on the podocyte, stabilising the actin cytoskeleton and therefore decreasing protein leak.Therefore tacrolimus (prograf) is likely to be effective in reducing proteinuria in minimal change disease.It has also been shown to have a good side effect profile when used to allow the avoidance of steroids in transplantation.This study aims to prospectively study if tacrolimus (prograf) is effective as treatment for minimal change disease compared with standard therapy with steroids, and whether it has advantages in terms of side effect profile and prevention of relapse.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 OHS
    • Hammersmith Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with nephrotic syndrome (hypoalbuminaemia and protein creatinine ratio (PCR) > 100units), secondary to minimal change disease.
• Age over 18.

Exclusion Criteria:

• Hepatitis B, hepatitis C or HIV infection.
• Untreated infection.
• Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception.
• Patients who have been treated with immunosuppression over the last 18 months.
• Patients who have had more than 3 relapses of nephrotic syndrome within 5 years.
• Any condition judged by the investigator that would cause the study to be detrimental to the patient.

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: prednisolone; prednisolone tablets	Drug: prednisolone; Prednisolone 1mg/kg maximum 60mg od
Experimental: tacrolimus; tacrolimus tablets	Drug: tacrolimus; tacrolimus0.05mg/kg bd (levels 6-12ng/ml); Other Names: prograff

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Complete Remission From Nephrotic Syndrome at 8 Weeks	normalisation of serum albumin and urine PCR <50 units	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks	16 and 26 weeks
Percentage of Patients Achieving Remission Who Then Relapse	2 years
Number of Serious Adverse Events	3 years
Change in Baseline Glomerular Filtration Rate	3 years

Collaborators and Investigators

• Sponsor: Imperial College Healthcare NHS Trust
• Investigators: Study Chair: Megan Griffith, MBChBPhDFRCP, Imperial College NHS Trust; Principal Investigator: Tom Cairns, MBBSMRCP, Imperial College NHS Trust

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.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2009
• Primary Completion (Actual): October 10, 2019
• Study Completion (Actual): October 10, 2019

Study Registration Dates

• First Submitted: September 21, 2009
• First Submitted That Met QC Criteria: September 21, 2009
• First Posted (Estimate): September 22, 2009

Study Record Updates

• Last Update Posted (Actual): May 4, 2021
• Last Update Submitted That Met QC Criteria: April 9, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: nephrotic minimal change tacrolimus prednisolone
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Nephrosis; Nephrosis, Lipoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Calcineurin Inhibitors; Prednisolone; Tacrolimus
• Other Study ID Numbers: 13HH1283; 2009-014292-52 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No