Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy

IGA Nephropathy Clinical Trial

— SIREPNA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00396721
• Other study ID #: SIREPNA/05
• Secondary ID: 2005-002610-37
• Status: Completed
• Phase: Phase 2
• First received: November 3, 2006
• Last updated: September 14, 2011
• Start date: January 2006
• Est. completion date: February 2010

Study information

• Verified date: September 2011
• Source: Hospital Universitari de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: February 2010
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glomerulonephritis
• Glomerulonephritis, IGA
• IGA Nephropathy
• Kidney Diseases
• Nephropathy, IGA

Intervention

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
• Sirolimus (study drug)+ACE inhibitor + statin
enalapril starting at 5 mg/d in order to control blood pressure. Atorvastatin starting at 10 mg/d

Locations

Country	Name	City	State
Spain	Nephrology Department. Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Josep m Cruzado	Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

Spain, 

References & Publications (4)

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. — View 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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change in the glomerular filtrate rate evaluated by means of radionuclide techniques (51Cr-EDTA) and comparison between both arms		At months 6th and 12th	No
Secondary	Change in renal histology		At 12 months	No
Secondary	Percentage of patients who withdraw from the study medication due to adverse events		Within 1 year	Yes
Secondary	Percentage of patients with therapeutic failure		Within 1 year	Yes

External Links

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