Tacrolimus Versus Prednisolone for the Treatment of Minimal Change Disease

Condition(s) targeted: Minimal Change Disease

Intervention: tacrolimus (Drug); prednisolone (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Imperial College Healthcare NHS Trust

Official(s) and/or principal investigator(s):
Megan Griffith, MBChBPhDFRCP, Study Chair, Affiliation: Imperial College NHS Trust
Tom Cairns, MBBSMRCP, Principal Investigator, Affiliation: Imperial College NHS Trust

Overall contact:
Megan Griffith, MbChBPhDFRCP, Phone: 02083835272, Email: m.e.griffith@imperial.ac.uk

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.

Official title: Tacrolimus vs Prednisolone for the Treatment Minimal Change Disease

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Proportion of patients achieving complete remission from nephrotic syndrome (normalisation of serum albumin and urine PCR <50 units) at 8 weeks

Secondary outcome:

Proportion of patients achieving complete remission from nephrotic syndrome at 16 and 24 weeks

Proportion of patients achieving remission who then relapse

Nature severity and frequency of adverse events

change in baseline glomerular filtration rate

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Megan Griffith, MbChBPhDFRCP, Phone: 02083835272, Email: m.e.griffith@imperial.ac.uk

Hammersmith Hospital, London W12 OHS, United Kingdom; Recruiting
Megan Griffith, MBChBFRCPPhD, Principal Investigator

Starting date: December 2009
Last updated: May 1, 2015