Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy (SIREPNA)

• ClinicalTrials.gov Identifier: NCT00396721
• Recruitment Status: Completed
• First Posted: November 7, 2006
• Last Update Posted: September 16, 2011
• Sponsor: Josep m Cruzado
• Collaborator: Wyeth is now a wholly owned subsidiary of Pfizer
• Information provided by (Responsible Party): Josep m Cruzado, Hospital Universitari de Bellvitge

Study Description

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

• 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

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

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

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• 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

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

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. doi: 10.1056/NEJMra020109. No abstract available.

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.

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.

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.

• Responsible Party: Josep m Cruzado, Nephrologist, Hospital Universitari de Bellvitge
• ClinicalTrials.gov Identifier: NCT00396721
• 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; 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