Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy (SIREPNA)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Glomerulonephritis, IGA; Nephropathy, IGA; IGA Nephropathy	Drug: ACE inhibitor + statin; Drug: Sirolimus (study drug)+ACE inhibitor + statin	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	23 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Pilot Trial of Treatment of Poor-Prognosis IgA Nephropathy With Low Exposure to Sirolimus.
Study Start Date :	January 2006
Actual Primary Completion Date :	October 2009
Actual Study Completion Date :	February 2010

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: A	Drug: ACE inhibitor + statin; 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
Experimental: B	Drug: Sirolimus (study drug)+ACE inhibitor + statin; enalapril starting at 5 mg/d in order to control blood pressure. Atorvastatin starting at 10 mg/d

Outcome Measures

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Primary Outcome Measures :

1. 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 [ Time Frame: at month 12th ]

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Spain
Nephrology Department. Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, Spain, 08907

Sponsors and Collaborators

Josep m Cruzado

Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

Study Chair:	Josep M Cruzado, Medical Doctor	Nephrlogy Department. Hospital Universitari de Bellvitge
Principal Investigator:	Meritxell Ibernon, MD	Germans Trias i Pujol Hospital
Principal Investigator:	JORDI BALLARÍN, MD	FUNDACIÓ PUIGVERT DE BARCELONA

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

This is the center in Spain for the central contact and the main location including patients. 

Publications:

Donadio JV, Grande JP. IgA nephropathy. N Engl J Med. 2002 Sep 5;347(10):738-48. Review.

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.

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.

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. Epub 2005 May 25.

Responsible Party:	Josep m Cruzado, Nephrologist, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier:	NCT00396721 History of Changes
Other Study ID Numbers:	SIREPNA/05; 2005-002610-37
First Posted:	November 7, 2006
Last Update Posted:	September 16, 2011
Last Verified:	September 2011

Keywords provided by Josep m Cruzado, Hospital Universitari de Bellvitge:

Nephropathy, IGA; Pilot trial; Sirolimus; Rapamune

Additional relevant MeSH terms:

Kidney Diseases; Glomerulonephritis, IGA; Glomerulonephritis; Urologic Diseases; Nephritis; Autoimmune Diseases; Immune System Diseases; Sirolimus; Everolimus; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Anti-Infective Agents	Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lipid Regulating Agents; Protease Inhibitors