Tacrolimus Versus Prednisolone for the Treatment of Minimal Change Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Tacrolimus vs Prednisolone for the Treatment Minimal Change Disease

Conditions
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Minimal Change Disease

Intervention / Treatment
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* Drug: tacrolimus
* Drug: prednisolone


Participation Criteria
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Eligibility Criteria
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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.

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

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nephrotic minimal change tacrolimus prednisolone