Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy

Study Overview
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Brief Summary
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The purpose of this study is to test in a pilot trial the efficacy and tolerance of sirolimus oral (at low doses) in patient to treat poor-prognosis IgA Nephropathy.

Official Title
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Pilot Trial of Treatment of Poor-Prognosis IgA Nephropathy With Low Exposure to Sirolimus.

Conditions
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Glomerulonephritis, IGA, Nephropathy, IGA, IGA Nephropathy

Intervention / Treatment
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* Drug: ACE inhibitor + statin
* Drug: Sirolimus (study drug)+ACE inhibitor + statin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 70 and with capacity to grant informed consent Biopsy-proven IgA nephropathy by means of standard immunohistochemical and morphological criteria Renal biopsy in the in the 3 months prior to randomization date Absence of known hepatic, cardiac, pulmonary or intestinal disease Glomerular filtrate estimated by Cockcroft-Gault, more than 30 ml/min Any of the following clinical states: a) High blood pressure defined as systolic blood pressure higher than 140 mmHg or diastolic blood pressure higher than 90 mmHg associated with proteinuria between 0.3-1 g/day and/or microhematuria. b) Proteinuria higher than 1g/day Women of child-bearing age will follow a suitable contraceptive method, and a negative pregnancy test will be needed before inclusion in the study Exclusion Criteria: Serology positive for HIV or hepatitis B infection (defined as positive for the HbsAg antigen) or hepatitis C infection (defined as viral RNA detection) Treatment with steroids or immunosuppressors in the two previous years Evidence of active infection at the time of inclusion in the study Pregnancy or breastfeeding at the time of inclusion in the study Estimated glomerular filtration < 30 ml/min, bilirubin > 2 mg/dl, or ALT or AST two times higher than the normal upper limit Diabetes Mellitus, defined as patients treated with insulin or oral antidiabetics or glycemias higher than 140 mg/dl in two or more episodes Poor control of high blood pressure (defined as systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg, taking 3 or more antihypertensives) or evidence or suspicion of renovascular disease Thrombocytopenia less than 100,000 /mm3 or total neutrophil value lower than 2000 /mm3 or triglycerides value > 400 mg/dL (4.6 mmol/L) or cholesterol > 300 mg/dL (7.8 mmol/L) or LDL > 200 mg/dL IgA nephropathy systemic forms, i.e., Schönlein-Henoch purpura, IgA nephropathy secondary forms, post-renal transplant IgA nephropathy recurrences, cases presented in the form of rapidly progressive renal failure and cases with the presence of cellular crescents in more than 50% of the glomeruli will be excluded History of cancer in the previous 5 years,exception of skin basocellular carcinoma and uterine in situ carcinoma (completely removed both of them) Know intolerance to Sirolimus or macrolides

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: A<br> | Drug: ACE inhibitor + statin<br>* sirolimus starting at 1 mg/d (target 3-6 ng/ml) plus enalapril starting at 5 mg/d to control blood pressure plus atorvastatin starting at 10 mg/d<br>|
| Experimental: B<br> | Drug: Sirolimus (study drug)+ACE inhibitor + statin<br>* enalapril starting at 5 mg/d in order to control blood pressure. Atorvastatin starting at 10 mg/d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of the administration of Rapamune on a clinical composite variable (change in proteinuria, blood pressure and hematuria) in patients with IgA nephropathy with poor prognosis criteria |  | at month 12th | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the glomerular filtrate rate evaluated by means of radionuclide techniques (51Cr-EDTA) and comparison between both arms |  | At months 6th and 12th | 
| Change in renal histology |  | At 12 months | 
| Percentage of patients who withdraw from the study medication due to adverse events |  | Within 1 year | 
| Percentage of patients with therapeutic failure |  | Within 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nephropathy, IGA, Pilot trial, Sirolimus, Rapamune