Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy

NCT ID: NCT00396721

Last Updated: 2011-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2010-02-28

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.

Conditions

Glomerulonephritis, IGA; Nephropathy, IGA; IGA Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Group Type: ACTIVE_COMPARATOR

ACE inhibitor + statin

Intervention Type: DRUG

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

B

Group Type: EXPERIMENTAL

Sirolimus (study drug)+ACE inhibitor + statin

Intervention Type: DRUG

enalapril starting at 5 mg/d in order to control blood pressure. Atorvastatin starting at 10 mg/d

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wyeth is now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

Josep m Cruzado

OTHER

Sponsor Role: lead

Responsible Party

Josep m Cruzado

Nephrologist

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Josep M Cruzado, Medical Doctor

Role: STUDY_CHAIR

Nephrlogy Department. Hospital Universitari de Bellvitge

Meritxell Ibernon, MD

Role: PRINCIPAL_INVESTIGATOR

Germans Trias i Pujol Hospital

JORDI BALLARÍN, MD

Role: PRINCIPAL_INVESTIGATOR

FUNDACIÓ PUIGVERT DE BARCELONA

Locations

Nephrology Department. Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Countries

Spain

References

Donadio JV, Grande JP. IgA nephropathy. N Engl J Med. 2002 Sep 5;347(10):738-48. doi: 10.1056/NEJMra020109. No abstract available.

Reference Type: BACKGROUND

PMID: 12213946 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7935657 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11576346 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15917339 (View on PubMed)

Related Links

http://www.bellvitgehospital.cat/

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

Other Identifiers

2005-002610-37

Identifier Type: -

Identifier Source: secondary_id

SIREPNA/05

Identifier Type: -

Identifier Source: org_study_id