Clinical trial NCT00396721: Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy
Official title: Pilot Trial of Treatment of Poor-Prognosis IgA Nephropathy With Low Exposure to Sirolimus.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glomerulonephritis, IGA
Nephropathy, IGA
IGA Nephropathy
Keywords: Nephropathy, IGA
Pilot trial
Sirolimus
Rapamune
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Wyeth is now a wholly owned subsidiary of Pfizer
First posted: 2006-11-07
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: at month 12th
Secondary outcomes:
measure: Change in the glomerular filtrate rate evaluated by means of radionuclide techniques (51Cr-EDTA) and comparison between both arms
timeFrame: At months 6th and 12th
measure: Change in renal histology
timeFrame: At 12 months
measure: Percentage of patients who withdraw from the study medication due to adverse events
timeFrame: Within 1 year
measure: Percentage of patients with therapeutic failure
timeFrame: Within 1 year
Other outcomes:
Locations:
city: L'Hospitalet de Llobregat
country: Spain
facility: Nephrology Department. Hospital Universitari de Bellvitge
state: Barcelona
Study officials:
affiliation: Nephrlogy Department. Hospital Universitari de Bellvitge
name: Josep M Cruzado, Medical Doctor
role: STUDY_CHAIR
affiliation: Germans Trias i Pujol Hospital
name: Meritxell Ibernon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: FUNDACIÓ PUIGVERT DE BARCELONA
name: JORDI BALLARÍN, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Donadio JV, Grande JP. IgA nephropathy. N Engl J Med. 2002 Sep 5;347(10):738-48. doi: 10.1056/NEJMra020109. No abstract available.
citation: Donadio JV Jr, Bergstralh EJ, Offord KP, Spencer DC, Holley KE. A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group. N Engl J Med. 1994 Nov 3;331(18):1194-9. doi: 10.1056/NEJM199411033311804.
citation: Wu H, Clarkson AR, Knight JF. Restricted gammadelta T-cell receptor repertoire in IgA nephropathy renal biopsies. Kidney Int. 2001 Oct;60(4):1324-31. doi: 10.1046/j.1523-1755.2001.00937.x.
citation: Bonegio RG, Fuhro R, Wang Z, Valeri CR, Andry C, Salant DJ, Lieberthal W. Rapamycin ameliorates proteinuria-associated tubulointerstitial inflammation and fibrosis in experimental membranous nephropathy. J Am Soc Nephrol. 2005 Jul;16(7):2063-72. doi: 10.1681/ASN.2004030180. Epub 2005 May 25.