Sirolimus Therapy for Poor Prognosis Immunoglobulin A Nephropathy

NCT00396721 | Completed Phase 2 DMC

• 2 other identifiers: SIREPNA/052005-002610-37
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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

Keywords

Nephropathy, IGA; Pilot trial; Sirolimus; Rapamune

Outcome Measures

Primary Outcomes (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

  at month 12th

Secondary Outcomes (4)

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

  At months 6th and 12th

• Change in renal histology

  At 12 months

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

  Within 1 year

• Percentage of patients with therapeutic failure

  Within 1 year

Study Arms (2)

A

ACTIVE COMPARATOR

Drug: ACE inhibitor + statin

B

EXPERIMENTAL

Drug: Sirolimus (study drug)+ACE inhibitor + statin

Interventions

ACE inhibitor + statin 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

A

Sirolimus (study drug)+ACE inhibitor + statin DRUG

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

B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Josep m Cruzado: lead
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (1)

Nephrology Department. Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Related Publications (4)

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

  PMID: 12213946 BACKGROUND

• 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.

  PMID: 7935657 BACKGROUND

• 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.

  PMID: 11576346 BACKGROUND

• 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.

  PMID: 15917339 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Glomerulonephritis, IGA

Interventions

Angiotensin-Converting Enzyme Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Sirolimus

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Lipid Regulating Agents; Therapeutic Uses; Macrolides; Lactones; Organic Chemicals

Study Officials

• Josep M Cruzado, Medical Doctor

  Nephrlogy Department. Hospital Universitari de Bellvitge

  STUDY CHAIR

• Meritxell Ibernon, MD

  Germans Trias i Pujol Hospital

  PRINCIPAL INVESTIGATOR

• JORDI BALLARÍN, MD

  FUNDACIÓ PUIGVERT DE BARCELONA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Nephrologist

Study Record Dates

• First Submitted: November 3, 2006
• First Posted: November 7, 2006
• Study Start: January 1, 2006
• Primary Completion: October 1, 2009
• Study Completion: February 1, 2010
• Last Updated: September 16, 2011

Record last verified: 2011-09

Locations

ES (1)