Pilot Study of Mycophenolate Mofetil in Congenital Uropathies
Congenital or hereditary structural anomalies of the genitourinary tract account for approximately half of all cases of end stage renal disease in the pediatric population. Despite optimal medical management, when the GFR falls below 50 ml/min/1.73 M2, nearly 40% of affected children will require dialysis or a renal transplant within 2 years. At present, there is no specific treatment for patients with congenital uropathies that can retard the progressive loss of kidney function and forestall the need for renal replacement therapy.
There is evidence in experimental animals and in patients with chronic renal failure (CRF) that immunoeffector mechanisms are activated within the renal parenchyma. Infiltration of the kidney by macrophages, monocytes, and lymphocytes, activation of renal tubular epithelial cells, and release of pro-inflammatory cytokines result in fibrosis and irreversible organ damage.
Mycophenolate mofetil (MMF) is a new immunosuppressive agent that is used to prevent acute rejection in kidney transplant recipients. It attenuates renal damage in the remnant kidney model of CRF in which there is no primary immunological injury. Therefore, this pilot study is designed to test the hypothesis that immunosuppressive treatment with MMF in children with structural causes of CRF will be safely tolerated and that this therapy will retard progressive decline in renal function.
Patients with congenital uropathy, 3-16 years of age and with a GFR less than 50 ml/ml/1.73 M2, will be treated with MMF for 24 months. The two primary endpoints are: (1) safety and tolerance of the drug; and (2) need for dialysis or kidney transplantation. It is anticipated that the MMF will be free of significant toxicity and that administration of the drug will reduce the frequency of progression to end stage renal disease from 38% to 19%. Patients will be followed at 3-month intervals and they will undergo serial assessment of proteinuria, estimated GFR and iothalamate clearance, urinary cytokine excretion, urine flow cytometry, and immunologic testing.
The significance of this pilot study is that it may provide evidence in support of a randomized, double-blind, placebo-controlled trial of immunological treatment of congenital structural causes of CRF in children
Congenital Urological Abnormalities
Drug: mycophenolate mofetil
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of Mycophenolate Mofetil in Congenital Uropathies|
- Reduction in GFR [ Time Frame: 24 month treatment period ]
- Safety and tolerance of MMF [ Time Frame: 24 month treatment period ]
|Study Start Date:||March 2002|
|Study Completion Date:||August 2007|
Active Comparator: 1
Drug: mycophenolate mofetil
oral drug administration
Other Name: Cellcept
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00193635
|United States, New Jersey|
|Robert Wood Johnson Medical center|
|New Brunswick, New Jersey, United States, 08903-0019|
|United States, New York|
|Schneider Children's Hospital|
|New Hyde Park, New York, United States, 11040|
|Cornell Weill Medical Center|
|New York, New York, United States, 10021-4873|
|Principal Investigator:||Howard Trachtman, MD||Schneider Children's Hospital of North Shore-LIJ Health System|