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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-003884-12 | EudraCT Number |
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| Name | Class |
|---|---|
| Istituto Di Ricerche Farmacologiche Mario Negri | OTHER |
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The natural course of extracapillary glomerulonephritis is severe leading to End-Stage Renal Disease (ESRD) or death in most cases. Despite immunosuppressive treatment, long-term renal outcome remains poor since active crescents usually progress to fibrotic scars with glomerular occlusion and disruption.In experimental models Angiotensin Converting Enzyme (ACE)-inhibitor therapy targeting the over-expression of angiotensin type 1 (AT1) receptors, that are responsible for dysregulated proliferation of parietal cell progenitors, blocks the formation of crescents and their fibrotic evolution. Should these drugs have similar effects in humans, ACE-inhibitor therapy on top of standard immunosuppression might be instrumental to prevent ESRD and promote renal function recovery in clinical practice.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lisinopril | Experimental | Patients will receive, in addition to standard immunosuppressive therapy, lisinopril starting with 5 mg/day, then progressively up-titrated to reach the maximum tolerable dose (target dose) for 18 months. |
|
| No intervention | No Intervention | Patients will receive only the standard immunosuppressive therapy. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lisinopril | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| The extent of extracapillary proliferation on light microscopy, measured as % of total glomeruli with proliferative lesions at post-treatment repeat biopsy. | Changes from baseline and 6 and 18 month. |
| Measure | Description | Time Frame |
|---|---|---|
| Expression of parietal cell proliferation markers at glomerular level, graded on a scale of 0 to 3 (0: no staining, 1: mild, 2: moderate, 3: strong diffuse | Changes from baseline and 6 and 18 month. | |
| Number of fibrosclerotic crescents | Changes from baseline and 6 and 18 month. |
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Inclusion Criteria:
Rapidly progressive renal failure associated with acute nephritic syndrome and/or nephrotic syndrome;
Histology evidence of extracapillary proliferation with less than 50% of sclerotic glomeruli and associated with:
Clinical indication to immunosuppressive therapy;
No specific indication to treatment with Renin Angiotensin System (RAS) inhibitors such as heart failure or coronary ischemic disease;
Written informed consent.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Barbara Ruggiero, MD | Contact | 0039 035 45351 | barbara.ruggiero@marionegri.it | |
| Ettore Sabadini, MD | Contact | esabadini@asst-pg23.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò | Recruiting | Ranica | Bergamo | 24020 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24578468 | Background | Hruskova Z, Honsova E, Berden AE, Rychlik I, Lanska V, Zabka J, Bajema IM, Tesar V. Repeat protocol renal biopsy in ANCA-associated renal vasculitis. Nephrol Dial Transplant. 2014 Sep;29(9):1728-32. doi: 10.1093/ndt/gfu042. Epub 2014 Feb 26. | |
| 19875807 | Background | Smeets B, Angelotti ML, Rizzo P, Dijkman H, Lazzeri E, Mooren F, Ballerini L, Parente E, Sagrinati C, Mazzinghi B, Ronconi E, Becherucci F, Benigni A, Steenbergen E, Lasagni L, Remuzzi G, Wetzels J, Romagnani P. Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis. J Am Soc Nephrol. 2009 Dec;20(12):2593-603. doi: 10.1681/ASN.2009020132. Epub 2009 Oct 29. |
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| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D005355 | Fibrosis |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D017706 | Lisinopril |
| ID | Term |
|---|---|
| D004151 | Dipeptides |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance | Changes from baseline and 6, 12 and 18 month. |
| ASST Papa Giovanni XXIII | Recruiting | Bergamo | 24147 | Italy |
|
| 21718676 | Background | Benigni A, Morigi M, Rizzo P, Gagliardini E, Rota C, Abbate M, Ghezzi S, Remuzzi A, Remuzzi G. Inhibiting angiotensin-converting enzyme promotes renal repair by limiting progenitor cell proliferation and restoring the glomerular architecture. Am J Pathol. 2011 Aug;179(2):628-38. doi: 10.1016/j.ajpath.2011.04.003. Epub 2011 Jun 2. |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |