Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy - Full Text View

Sponsors and Collaborators:	Hospital Universitari de Bellvitge Wyeth
Information provided by:	Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier:	NCT00396721

Purpose

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	Intervention	Phase
Glomerulonephritis, IGA Nephropathy, IGA IGA Nephropathy	Drug: sirolimus + ACE inhibitor + statin Drug: ACE inhibitor + statin	Phase II

MedlinePlus related topics: Statins

Drug Information available for: Sirolimus

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Pilot Trial of Treatment of Poor-Prognosis IgA Nephropathy With Low Exposure to Sirolimus.

Further study details as provided by Hospital Universitari de Bellvitge:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
Change in renal histology [ Time Frame: At 12 months ] [ Designated as safety issue: No ]
Percentage of patients who withdraw from the study medication due to adverse events [ Time Frame: Within 1 year ] [ Designated as safety issue: Yes ]
Percentage of patients with therapeutic failure [ Time Frame: Within 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	January 2006
Estimated Study Completion Date:	September 2009
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator	Drug: ACE inhibitor + statin enalapril starting at 5 mg/d in order to control blood pressure. Atorvastatin starting at 10 mg/d
B: Experimental	Drug: sirolimus + 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

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
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 Cockroft-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 lactancy 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 glucaemias 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 macrolids

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00396721

Locations

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

Sponsors and Collaborators

Hospital Universitari de Bellvitge

Wyeth

Investigators

Study Chair:	Josep M Cruzado, Medical Doctor	Nephrlogy Department. Hospital Universitari de Bellvitge
Principal Investigator:	Jordi Ara, MD	HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL
Principal Investigator:	JORDI BALLARÍN, MD	FUNDACIÓ PUIGVERT DE BARCELONA

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

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

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:	Hospital Universitari de Bellvitge ( Josep M Cruzado )
Study ID Numbers:	SIREPNA/05, 2005-002610-37
Study First Received:	November 3, 2006
Last Updated:	January 27, 2009
ClinicalTrials.gov Identifier:	NCT00396721 History of Changes
Health Authority:	Spain: Ministry of Health

Keywords provided by Hospital Universitari de Bellvitge:

Nephropathy, IGA
Pilot trial
Sirolimus
Rapamune

Study placed in the following topic categories:

Sirolimus
Glomerulonephritis
Autoimmune Diseases
Immunologic Factors
Clotrimazole
Miconazole
Tioconazole
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Immunosuppressive Agents
Protease Inhibitors
Anti-Bacterial Agents
Immunoglobulin A

Enalapril
Antibodies
Enalaprilat
Urologic Diseases
Antifungal Agents
Nephritis
Glomerulonephritis, IGA
Angiotensin-Converting Enzyme Inhibitors
Kidney Diseases
Berger Disease
Atorvastatin
Immunoglobulins

Additional relevant MeSH terms:

Sirolimus
Anti-Infective Agents
Glomerulonephritis
Autoimmune Diseases
Immunologic Factors
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic

Immunosuppressive Agents
Pharmacologic Actions
Protease Inhibitors
Anti-Bacterial Agents
Urologic Diseases
Antifungal Agents
Therapeutic Uses
Nephritis
Glomerulonephritis, IGA
Angiotensin-Converting Enzyme Inhibitors
Kidney Diseases

ClinicalTrials.gov processed this record on May 07, 2009