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Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy (SIREPNA)

Primary Purpose

Glomerulonephritis, IGA, Nephropathy, IGA, IGA Nephropathy

Status

Completed

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

ACE inhibitor + statin

Sirolimus (study drug)+ACE inhibitor + statin

About this trial

This is an interventional treatment trial for Glomerulonephritis, IGA focused on measuring Nephropathy, IGA, Pilot trial, Sirolimus, Rapamune

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Nephrology Department. Hospital Universitari de Bellvitge

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm Description

Outcomes

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

Secondary Outcome Measures

Change in the glomerular filtrate rate evaluated by means of radionuclide techniques (51Cr-EDTA) and comparison between both arms

Change in renal histology

Percentage of patients who withdraw from the study medication due to adverse events

Percentage of patients with therapeutic failure

Full Information

NCT ID

NCT00396721

First Posted

November 3, 2006

Last Updated

September 14, 2011

Sponsor

Josep m Cruzado

Collaborators

Wyeth is now a wholly owned subsidiary of Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT00396721

Brief Title

Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy

Acronym

SIREPNA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2011

Overall Recruitment Status

Completed

Study Start Date

January 2006 (undefined)

Primary Completion Date

October 2009 (Actual)

Study Completion Date

February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Josep m Cruzado

Collaborators

Wyeth is now a wholly owned subsidiary of Pfizer

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glomerulonephritis, IGA, Nephropathy, IGA, IGA Nephropathy

Keywords

Nephropathy, IGA, Pilot trial, Sirolimus, Rapamune

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Title

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

ACE inhibitor + statin

Intervention Description

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

Intervention Name(s)

Sirolimus (study drug)+ACE inhibitor + statin

Intervention Description

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

Primary Outcome Measure Information:

Title

Time Frame

at month 12th

Secondary Outcome Measure Information:

Title

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

Title

Change in renal histology

Time Frame

At 12 months

Title

Percentage of patients who withdraw from the study medication due to adverse events

Time Frame

Within 1 year

Title

Percentage of patients with therapeutic failure

Time Frame

Within 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Josep M Cruzado, Medical Doctor

Organizational Affiliation

Nephrlogy Department. Hospital Universitari de Bellvitge

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Meritxell Ibernon, MD

Organizational Affiliation

Germans Trias i Pujol Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

JORDI BALLARÍN, MD

Organizational Affiliation

FUNDACIÓ PUIGVERT DE BARCELONA

Official's Role

Principal Investigator

Facility Information:

Facility Name

Nephrology Department. Hospital Universitari de Bellvitge

City

L'Hospitalet de Llobregat

State/Province

Barcelona

ZIP/Postal Code

08907

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

12213946

Citation

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

Results Reference

background

PubMed Identifier

7935657

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. doi: 10.1056/NEJM199411033311804.

Results Reference

background

PubMed Identifier

11576346

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. doi: 10.1046/j.1523-1755.2001.00937.x.

Results Reference

background

PubMed Identifier

15917339

Citation

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.

Results Reference

background

Links:

URL

http://www.bellvitgehospital.cat/

Description

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

Learn more about this trial

Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy

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