ACE-inhibitors in Extracapillary Glomerulonephritis

NCT02682459 | Unknown Phase 2

• 2 other identifiers: EXTRA2015-003884-12
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Extracapillary Glomerulonephritis

Keywords

Extracapillary glomerulonephritis; crescentic glomerulonephritis; rapidly progressive renal failure; chronic kidney disease; ACE-inhibitors; fibrosis

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (3)

• 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.

• Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance

  Changes from baseline and 6, 12 and 18 month.

Study Arms (2)

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.

Drug: Lisinopril

No intervention

NO INTERVENTION

Patients will receive only the standard immunosuppressive therapy.

Interventions

Lisinopril DRUG

Lisinopril

Eligibility Criteria

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

You may qualify if:

• 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:
• Type I: Anti-Glomerular Basement Membrane (GBM) antibody glomerulonephritis,
• Type II: Pauci-immune vasculitis or Anti Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis;
• Type III: Immune-complex mediated glomerular diseases: Proliferative lupus nephritis (LN), IgA nephropathy (IgAN)/ Schönlein-Henoch purpura, Type I membranoproliferative glomerulonephropathy (MPGN), Primary or secondary membranous nephropathy (MN), Primary or idiopathic immune complex glomerulonephritis.
• 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.

You may not qualify if:

• Pre-existing advanced chronic renal failure (creatinine clearance less than 20 ml/min/1.73m2);
• Evidence of B or C virus active infection;
• HIV infection;
• Recent diagnosis of malignancy;
• Prolonged bleeding time and any other contraindication to kidney biopsy evaluation;
• Any specific contraindication to ACE inhibitor therapy (that is: history of angioedema or other treatment-related serious adverse events);
• Pregnancy or lactating;
• Women of childbearing potential without following a scientifically accepted form of contraception;
• Inability to understand the risks and benefit of the study or evidence of an uncooperative attitude;
• Legal incapacity.

Sponsors & Collaborators

• Monia Lorini: lead
• Istituto Di Ricerche Farmacologiche Mario Negri: collaborator

Study Sites (2)

Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò

Ranica, Bergamo, 24020, Italy

RECRUITING

ASST Papa Giovanni XXIII

Bergamo, 24147, Italy

RECRUITING

Related Publications (3)

• 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.

  PMID: 24578468 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.

  PMID: 19875807 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.

  PMID: 21718676 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Fibrosis

Interventions

Lisinopril

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Barbara Ruggiero, MD

CONTACT

0039 035 45351; barbara.ruggiero@marionegri.it

Ettore Sabadini, MD

CONTACT

esabadini@asst-pg23.it

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: EC Secretary

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: February 15, 2016
• Study Start: February 1, 2016
• Primary Completion: September 1, 2019
• Study Completion: December 1, 2019
• Last Updated: April 6, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)